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Abstracts

Vitamin B6: 457 Research Abstracts

J Am Coll Nutr. 1999 Dec;18(6):582-90. Intakes of vitamin C, vegetables and fruits: which schoolchildren are at risk?

Hampl JS, Taylor CA, Johnston CS.

Graduate Program in Human Nutrition, Arizona State University, Tempe 85287-2502, USA.

OBJECTIVE: The purpose of this study was to determine vitamin C intakes among American schoolchildren. We investigated the leading sources of vitamin C in children's diets, the leading vegetables and fruits consumed by children and differences in dietary intake associated with vitamin C consumption. METHODS: Data from 1,350 7- to 12-year-old and 908 13- to 18-year-old schoolchildren were obtained from the 1994-1996 Continuing Survey of Food Intakes by Individuals (CSFII). The children were stratified by age and gender and then split into three vitamin C consumption groups based upon two 24-hour recalls: low (0 to 30.0 mg), marginal (30.1 to 59.9 mg), and desirable (>60.0 mg). Data were analyzed by tabulation and by ANOVA followed by post hoc Scheffe's test. Outcome measures included food groups and energy-adjusted intakes of micro- and macronutrients. RESULTS: Among the 7- to 12-year-olds, 12% of boys and 13% of girls had mean vitamin C intakes that were less than 30 mg/day, and, among 13- to 18-year-olds, 14% of boys and 20% of girls had low vitamin C intakes. In addition to consuming significantly more vitamin C, children with desirable vitamin C intakes also consumed significantly more (p <0.001) energy-adjusted folate and vitamin B6; children with low vitamin C intakes tended to have significantly greater (p <0.001) energy-adjusted intakes of fat and saturated fat. Children with desirable vitamin C intakes consumed significantly more (p <0.006) high-vitamin C fruit juice, low-vitamin C vegetables and whole milk. Children with low vitamin C intakes on average consumed two daily servings of vegetables and fruits, of which less than 1/5 of a serving was citrus, while children with desirable vitamin C intakes consumed an average of one daily serving of citrus. CONCLUSIONS: A considerable number of children drastically under-consumed vitamin C and total vegetables and fruits. Overall, children with desirable vitamin C intakes had healthier diets, including more milk and vegetables, than did their peers with low vitamin C intakes. Health care professionals should continue to promote at least five daily servings of vegetables and fruits and should advise parents that at least one of these should be rich in vitamin C.

J Am Acad Nurse Pract. 2003 Jan;15(1):18-22.

Carpal tunnel syndrome: current theory, treatment, and the use of B6.

Holm G, Moody LE.

University of South Florida, USA. dr.g.holm@usfaccess.com

PURPOSE: To present the current state of the science of pathophysiology, assessment and treatment of carpal tunnel syndrome, including the use of pyridoxine (B6). DATA SOURCES: Selected research articles, texts, Websites, personal communications with experts, and the authors' own clinical experience. CONCLUSIONS: Much is yet to be learned about carpal tunnel syndrome. While the basic treatment of NSAIDs and nighttime splints seems universally accepted, much controversy remains. The use of vitamin B6 as a treatment is one such controversy requiring further investigation. IMPLICATIONS FOR PRACTICE: Current treatment for carpal tunnel syndrome should include NSAIDs, nighttime splinting, ergonomic workstation review, and vitamin B6 200 mg per day.

Eur J Clin Nutr. 2002 Nov;56(11):1087-93. Biochemical deficiency of pyridoxine does not affect interleukin-2 production of lymphocytes from patients with Sjogren's syndrome.

Tovar AR, Gomez E, Bourges H, Ortiz V, Kraus A, Torres N.

Department of Physiology of Nutrition, Instituto Nacional de Ciencias Medicas y Nutricion, Mexico, Mexico. artovar@quetzal.innsz.mx

BACKGROUND: There is evidence that pyridoxine deficiency may alter the immune response. It is not known whether a deficiency of this vitamin is evident in subjects with primary Sjogren's syndrome (SS). OBJECTIVE: We studied whether subjects with primary SS showed a biochemical deficiency of pyridoxine, and if it is associated with abnormal production of interleukin-2 from lymphocytes stimulated in vitro with phytohemagglutinin (PHA). DESIGN: Two studies were conducted, (i) biochemical and nutritional assessments were performed in a cross-over study in subjects with primary SS, who were supplemented with 25 mg/day of pyridoxine or placebo for 3 months. After 1 month washout, they were supplemented for 3 months with placebo, (ii) patients with SS and matched controls received pyridoxine or placebo for 45 days, and a blood sample was obtained to study IL-2 production and expression in T-lymphocytes stimulated with PHA. RESULTS: Subjects with primary SS showed limited dietary intake of pyridoxine and biochemical deficiency of this vitamin assessed through the activation coefficient of the erythrocyte aspartate aminotransferase. The biochemical deficiency did not affect production nor mRNA expression of IL-2 from T-lymphocytes stimulated in vitro with PHA compared with the control group. Supplementation of subjects with primary SS with 25 mg/day with pyridoxine for 45 days did not produce any significant change as compared to those patients supplemented with placebo. CONCLUSIONS: Subjects with primary SS showed biochemical deficiency of pyridoxine, possibly due to limited intake of this vitamin which was corrected by supplementation with pyridoxine. However, IL-2 production and mRNA expression from stimulated lymphocytes were unaffected by supplementation, probably because the deficiency was not severe enough to affect the immune system. SPONSORSHIP: This work was supported by the National Council of Science and Technology (CONACYT), Mexico, grant no. 212226-5-0902PM.

J Trop Pediatr. 2002 Oct;48(5):303-6.

Pyridoxine-dependent seizures: long-term follow-up of two cases with clinical and MRI findings, and pyridoxine treatment.

Ulvi H, Mungen B, Yakinci C, Yoldas T.

Firat University Medical Faculty, Department of Neurology, Elazig, Turkey. hizirulvi@yahoo.com

Pyridoxine-dependency is a rare autosomal recessive disorder causing a severe seizure disorder of neonatal onset. There are a few reports including neuroimaging studies, such as cranial CT and MRI, and one report with longitudinal MRI findings in two cases with pyridoxine-dependent seizures (PDS). We report long-term follow-up of two siblngs with PDS in the light of clinical, EEG, CT and MRI findings, and pyridoxine treatment. The first patient, an 8-year-old female who had neonatal seizures, has sequential cranial CT and MRIs which are normal except for mega cistema magna thus far. She still has mild mental retardation, although the accurate diagnosis was made when she was 6 years old and pyridoxine treatment was initiated. The second patient, a 1-year-old female, who is the younger sibling of the first patient, presented with neonatal seizures and PDS was diagnosed immediately, with resulting pyridoxine treatment (10 mg/kg/day). She is now neurologically normal, seizure-free, and has sequential normal CT and MRIs. These patients show rather benign clinical courses

Seizure. 2002 Sep;11(6):381-3. Add-on treatment with pyridoxine and sulthiame in 12 infants with West syndrome: an open clinical study.

Debus OM, Kohring J, Fiedler B, Franssen M, Kurlemann G.

University Children's Hospital, Department of Neuropediatrics, Westfalische-Wilhelms-Universitat Munster, Albert-Schweitzer-Str. 33, D - 48149 Munster, Germany. debuso@uni-muenster.de

To investigate the effect of sulthiame (STM) in West syndrome (WS) an open, uncontrolled add-on study was undertaken during initial pyridoxine (PDX) therapy in 12 infants, two with idiopathic and ten with symptomatic WS. All patients were initially treated with PDX (150-300 mg x kg (-1)body weight day(-1) ). In seven patients (58%) seizures and hypsarrhythmia stopped during the week after introduction of STM (10 mg x kg (-1)body weight day (-1)). In one the positive effect was temporary. Five of the responders (42%) remained seizure-free and without hypsarrhythmia under STM monotherapy, while one developed complex partial seizures after 25 months. STM was most effective in idiopathic WS (2 /2). During treatment with STM medication no patient suffered side effects attributable to the substance. Further controlled studies are necessary to evaluate the benefit of this potentially effective treatment.

Alcohol Clin Exp Res. 2002 Mar;26(3):340-6. Metadoxine in acute alcohol intoxication: a double-blind, randomized, placebo-controlled study.

Shpilenya LS, Muzychenko AP, Gasbarrini G, Addolorato G.

Narcological County Dispensary, Vasyleostrovsky District 4.th, Line V. 0.2 3-2 5, St. Petersburg, Russia.

BACKGROUND: At present there are only intriguing and preliminary clinical results regarding the efficacy of metadoxine (pyridoxol L-2-pyrrolidone-5-carboxylate) in acute alcohol intoxication. The present study was planned with the aim of investigating the effectiveness of metadoxine in the management of patients affected by acute ethanol intoxication. METHODS: A double-blind, randomized, multicenter, placebo-controlled trial was carried out on 58 patients of both sexes with acute ethanol intoxication. Patients were treated with a single dose of 900-mg intravenous metadoxine (n = 29) or with placebo (n = 29). Patients were clinically and biochemically evaluated at 0.5, 1, 2, 3, 6, 9, and 12 hr after treatment. RESULTS: Treatment with metadoxine significantly decreased the half-life of ethanol in blood (from 6.70 +/- 1.84 to 5.41 +/- 1.99 hr; p < 0.013) and showed a faster rate of ethanol elimination. The effects on ethanol half-life in blood were accompanied by a faster onset of recovery from intoxication, defined as the time of the transition of blood ethanol levels to the immediately lower range defined by intoxication categories (in g/liter: 0 to 0.5, absent; 0.51 to 1.0, mild; 1.1 to 2.5, moderate; >2.5, severe). Thus the median time to onset of recovery was 0.95 hr with metadoxine and 2.34 hr with placebo (p = 0.013). The effects of treatment on blood alcohol levels were paralleled by a significant decrease in the rating of the toxic clinical symptomatology. At 2 hr the improvement of toxic symptoms (in percent of maximum possible) was 68 +/- 28 vs. 44 +/- 27% in controls (p < 0.002). CONCLUSIONS: In patients with acute ethanol intoxication metadoxine accelerated the elimination of ethanol from blood, which led to faster recovery from intoxication, and improved the behavioral toxic symptomatology. Metadoxine could be helpful in the management of acute ethanol intoxication.

J Child Neurol. 2002 Mar;17(3):222-4.

Pyridoxine-dependent seizures associated with hypophosphatasia in a newborn.

Nunes ML, Mugnol F, Bica I, Fiori RM.

Division of Neurology, Hospital Sao Lucas, PUCRS School of Medicine, Porto Alegre-RS, Brazil. nunes@pucrs.br

Pyridoxine dependency and congenital hypophosphatasia are unusual metabolic disorders. We report a female infant born from healthy consanguineous parents with shortening of limbs, detected during pregnancy by ultrasonography. Immediately after delivery, the baby was admitted to the neonatal intensive care unit because of respiratory distress. A bone radiograph showed hypomineralization of all bones, and serum alkaline phosphatase was very low (10 U/L). Within the first day of life, seizures (focal clonic and tonic) started. The seizures were refractory to phenobarbital and other antiepileptic drugs. The first electroencephalogram (EEG) showed a burst-suppression pattern. Pyridoxine was administered (50 mg/kg) and completely controlled the seizures. Antiepileptic drugs were discontinued, and a maintenance dose of pyridoxine (10 mg/day) was established. A postpyridoxine EEG revealed the disappearance of the burst-suppression pattern. The patient died at age 26 days. Pyridoxine-dependent seizures, when recognized early and treated, have a more favorable prognosis. However, hypophosphatasia detected at birth almost always has a lethal outcome.

Pediatr Neurol. 2002 Mar;26(3):181-5. Pyridoxine-dependent seizures: findings from recent studies pose new questions.

Gospe SM.

Division of Pediatric Neurology, Department of Neurology, University of Washington, and Children's Hospital and Regional Medical Center, Seattle, WA 98105, USA.

Pyridoxine-dependent seizures, although a rare clinical entity, have been recognized as an etiology of intractable seizures in neonates and infants for more than 45 years. Recent research has focused on the molecular and neurochemical aspects of this disorder, as well as the optimal treatment of the condition. This review discusses the clinical features and management of patients with pyridoxine-dependent seizures together with a new hypothesis suggesting that an abnormality of pyridoxine transport may underlie the pathophysiology of this autosomal-recessive disorder.

N Engl J Med. 2001 Nov 29;345(22):1593-600.

Comment in: • N Engl J Med. 2002 Apr 4;346(14):1093-5. • N Engl J Med. 2002 Apr 4;346(14):1093-5. Decreased rate of coronary restenosis after lowering of plasma homocysteine levels.

Schnyder G, Roffi M, Pin R, Flammer Y, Lange H, Eberli FR, Meier B, Turi ZG, Hess OM.

Division of Cardiology, Swiss Cardiovascular Center Bern, University Hospital. g.schnyder@lycos.com

BACKGROUND: We have previously demonstrated an association between elevated total plasma homocysteine levels and restenosis after percutaneous coronary angioplasty. We designed this study to evaluate the effect of lowering plasma homocysteine levels on restenosis after coronary angioplasty. METHODS: A combination of folic acid (1 mg), vitamin B12 (400 microg), and pyridoxine (10 mg)--referred to as folate treatment--or placebo was administered to 205 patients (mean [+/-SD] age, 61+/-11 years) for six months after successful coronary angioplasty in a prospective, double-blind, randomized trial. The primary end point was restenosis within six months as assessed by quantitative coronary angiography. The secondary end point was a composite of major adverse cardiac events. RESULTS: Base-tine characteristics and initial angiographic results after coronary angioplasty were similar in the two study groups. Folate treatment significantly lowered plasma homocysteine levels from 11.1+/-4.3 to 7.2+/-2.4 micromol per liter (P<0.001). At follow-up, the minimal luminal diameter was significantly larger in the group assigned to folate treatment (1.72+/-0.76 vs. 1.45+/-0.88 mm, P=0.02), and the degree of stenosis was less severe (39.9+/-20.3 vs. 48.2+/-28.3 percent, P=0.01). The rate of restenosis was significantly lower in patients assigned to folate treatment (19.6 vs. 37.6 percent, P=0.01), as was the need for revascularization of the target lesion (10.8 vs. 22.3 percent, P=0.047). CONCLUSIONS: Treatment with a combination of folic acid, vitamin B12, and pyridoxine significantly reduces homocysteine levels and decreases the rate of restenosis and the need for revascularization of the target lesion after coronary angioplasty. This inexpensive treatment, which has minimal side effects, should be considered as adjunctive therapy for patients undergoing coronary angioplasty

Am J Psychiatry. 2001 Sep;158(9):1511-4. Vitamin B(6) in the treatment of tardive dyskinesia: a double-blind, placebo-controlled, crossover study.

Lerner V, Miodownik C, Kaptsan A, Cohen H, Matar M, Loewenthal U, Kotler M.

Division of Psychiatry, Ministry of Health Be'er Sheva Mental Health Center, Faculty of Health Sciences Ben-Gurion University of the Negev, Israel. lernervld@yahoo.com

OBJECTIVE: The authors' goal was to conduct a double-blind trial of vitamin B(6) in the treatment of tardive dyskinesia in patients with schizophrenia. METHOD: Fifteen inpatients with schizophrenia who met research diagnostic criteria for tardive dyskinesia were randomly assigned to treatment with either vitamin B(6) or placebo for 4 weeks in a double-blind crossover paradigm. The Extrapyramidal Symptom Rating Scale was used to assess patients weekly. RESULTS: Mean scores on the parkinsonism and dyskinetic movement subscales of the Extrapyramidal Symptom Rating Scale were significantly better in the third week of treatment with vitamin B(6) than during the placebo period. CONCLUSIONS: Vitamin B(6) appears to be effective in reducing symptoms of tardive dyskinesia.

J Heart Lung Transplant. 2001 Sep;20(9):964-9. Pyridoxine improves endothelial function in cardiac transplant recipients.

Miner SE, Cole DE, Evrovski J, Forrest Q, Hutchison S, Holmes K, Ross HJ.

Department of Medicine, University of Toronto, Toronto, Ontario, Canada.

BACKGROUND: Endothelial dysfunction is common in cardiac transplant recipients and predicts the development of transplant coronary artery disease. Hyperhomocysteinemia is associated with endothelial dysfunction in the general population, is common in transplant recipients, and has been associated with transplant coronary artery disease. Thus therapy that decreases homocysteine concentrations might also improve endothelial function and decrease the risk of transplant coronary artery disease. Folate and pyridoxine are important cofactors in distinct aspects of homocysteine metabolism. The purpose of this study was to determine whether folate or pyridoxine supplementation improves endothelial function in cardiac transplant recipients. METHODS AND RESULTS: This was a double-blind, randomized, placebo-controlled trial. We assigned 31 transplant recipients to either pyridoxine (n = 11:100 mg/day), folate (n = 12:5 mg/day), or placebo (n = 8) for 10 weeks. Fasting and post-methionine-load (methionine 100 mg/kg orally) homocysteine concentrations were determined. Brachial artery flow-mediated dilatation was used as a measure of endothelial function. At follow-up, we noted no significant changes in homocysteine concentrations in any of the groups. However, pyridoxine supplementation was associated with a significant improvement in endothelial function (2.8 +/- 6.7 to 6.9 +/- 6.3, p = 0.05). No significant changes were seen in patients treated with folate or placebo. CONCLUSIONS: Pyridoxine, but not folate supplementation, significantly improves endothelial function in cardiac transplant recipients.

Vestn Oftalmol. 2001 Sep-Oct;117(5):37-40.

[Prognostic significance of local and systemic indicators of lipid peroxidation and antioxidant system in perforating wounds of the eyes and their time course during local antioxidant treatment]

[Article in Russian]

Arkhipova LT, Dolgova IG.

Lipid peroxidation parameters malonic dialdehyde (MDA) and dienic conjugates (DC) and antioxidant defense (AOD) values superoxide dismutase (SOD), catalase, alpha-tocopherol were measured in the blood neutrophils and lacrimal fluid of 66 patients on days 1-2, 7-8, 14-15, and 21-22 after perforating wound of first, second, third, and fourth degree of severity according to P, 1. Lebekhov and in repeated injury, and the time course of these parameters during local treatment with therapeutic films with emoxipin and emoxipin + piridoxine was evaluated. A stable increase of MDA and DC levels in blood neutrophils, decrease of catalase, SOD, and alpha-tocopherol levels in blood neutrophils, and decrease of catalase enzymes and SOD activities in the lacrimal fluid of injured eye starting from days 7-8 are prognostically unfavorable signs. These data prompt the use of local and systemic treatment with antioxidants (emoxipin, tocopherol, etc.) in perforating wounds starting from the first days after the injury. Good clinical and antioxidant effect was observed after treatment with ocular therapeutic films with emoxipin and piridoxine.

J Clin Pharmacol. 2001 Aug;41(8):842-5. The safety of higher than standard dose of doxylamine-pyridoxine (Diclectin) for nausea and vomiting of pregnancy.

Atanackovic G, Navioz Y, Moretti ME, Koren G.

Division of Clinical Pharmacology/Toxicology, Hospital for Sick Children, Toronto, Canada.

A delayed-release combination of doxylamine-pyridoxine (D-P) (Diclectin) is the only approved antiemetic medication for use in pregnancy in Canada. The standard recommended dose is up to 4 tablets a day, regardless of body weight or severity of symptoms. The objective of this study was to determine the incidence of adverse maternal and fetal effects and pregnancy outcome in 225 women taking Diclectin at the recommended (n = 123) or higher than recommended (n = 102) doses. In this observational, prospective study, one-third (33.6%) of women reported having adverse effects (sleepiness, tiredness, and/or drowsiness) temporally related to the medication. There was no association between the dose per kg and rates of reported maternal adverse effects with doses ranging from 0.1 mg/kg to 2.0 mg/kg (1-12 tablets). Nausea and vomiting of pregnancy (NVP) was reported as severe by the majority (75.8%) of women. Mean birth weight (BW) was 3,400 g and gestational age (GA) 39 weeks. Multivariate analysis revealed that only prepregnancy weight and GA predicted lower BW, not the dose of D-P or the severity of NVP. There were two pregnancies with major malformation, a finding that is consistent with the rates of birth defects in the general population. It was concluded that the higher than standard dose of Diclectin, when calculated per kg of body weight, does not affect either the incidence of maternal adverse effects or pregnancy outcome. If needed, Diclectin can be given at doses higher than 4 tablets/day to normalize for body weight or optimize efficacy.

J Nutr. 2001 Aug;131(8):2204-7. Vitamin B-6-supplemented diets compared with a low vitamin B-6 diet suppress azoxymethane-induced colon tumorigenesis in mice by reducing cell proliferation.

Komatsu SI, Watanabe H, Oka T, Tsuge H, Nii H, Kato N.

Faculty of Applied Biochemistry, Hiroshima University, Higashi-Hiroshima 739-8528, Japan.

Male ICR mice were examined for the effect of vitamin B-6 [pyridoxine (PN) HCl] on azoxymethane-induced colon tumorigenesis. Mice were fed the diets containing 1, 7, 14 or 35 mg PN HCl/kg for 22 wk, and given a weekly injection of azoxymethane (5 mg/kg body) for the initial 10 wk. Compared with the 1 mg PN HCl/kg diet, 7, 14 and 35 mg PN HCl/kg diets significantly suppressed the incidence and number of colon tumors, colon cell proliferation and expressions of c-myc and c-fos proteins. For some variables, 14 and 35 mg PN HCl/kg diets were more effective than the 7 mg/kg diet. Supplemental vitamin B-6 had no influence on the number of colon apoptotic cells. The results suggest that elevating dietary vitamin B-6 suppresses colon tumorigenesis by reducing cell proliferation.

J Nutr. 2001 Jun;131(6):1777-86.

Erratum in: • J Nutr 2001 Aug;131(8):2224. Assessment of vitamin B-6 status in young women consuming a controlled diet containing four levels of vitamin B-6 provides an estimated average requirement and recommended dietary allowance.

Hansen CM, Shultz TD, Kwak HK, Memon HS, Leklem JE.

Department of Food Science and Human Nutrition, Washington State University, Pullman, WA 99164-6376, USA.

The Recommended Dietary Allowance (RDA) of vitamin B-6 for young women was recently reduced from 1.6 to 1.3 mg/d based on an adequate plasma pyridoxal phosphate (PLP) concentration of 20 nmol/L. To assess vitamin B-6 requirements and suggest recommendations for intake, seven healthy young women consumed a controlled diet providing 1.2 g protein/kg body weight for a 7-d adjustment period (1.0 mg vitamin B-6/d) and three successive 14-d experimental periods (1.5, 2.1 and 2.7 mg/d, respectively). Direct and indirect vitamin B-6 status indicators were measured in plasma, erythrocytes and urine. Indicators most strongly correlated with vitamin B-6 intake [i.e., plasma and erythrocyte PLP, urinary 4-pyridoxic acid (4-PA) and total vitamin B-6] were regressed on vitamin B-6 intake and the dietary vitamin B-6 to protein ratio. Inverse prediction using adequate and baseline values estimated vitamin B-6 requirement. Adequate values were determined for plasma PLP and urinary 4-PA from baseline values of 60 previous subjects, using the statistical method suggested by Sauberlich. The current study suggests a vitamin B-6 Estimated Average Requirement (EAR) for young women of 1.1 mg/d or 0.016 mg/g protein, and a RDA of 1.5 mg/d or 0.020 mg/g protein. When results from this study are combined with data from four other recent studies, the combined data predict an EAR of 1.2 mg/d or 0.015 mg/g protein, and a RDA of 1.7 mg/d or 0.018 mg/g protein. This study suggests that the current vitamin B-6 RDA may not be adequate.

Harefuah. 2001 May;140(5):369-73, 456.

[Antidepressive effect of pyridoxine (vitamin B6) in neuroleptic-treated schizophrenic patients with co-morbid minor depression--preliminary open-label trial]

[Article in Hebrew]

Shiloh R, Weizman A, Weizer N, Dorfman-Etrog P, Munitz H.

Geha Psychiatric Hospital, Felsenstein Medical Research Center, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel.

BACKGROUND: Minor depression is reported in 20-60% of schizophrenic patients during various stages of their disorders; impairing patients' compliance, response to treatment and worsening their overall prognosis. Various anti-depressive treatments have been proposed for such cases but response rates are usually poor. Pyridoxine (Vitamin B6) in essential for the proper metabolism of various neurotransmitters that are considered relevant to the pathophysiology of depression and/or schizophrenia and it has been reported beneficial in ameliorating depressive symptoms as part of major depression, premenstrual syndrome or 'Chinese restaurant syndrome'. We hypothesized that addition of pyridoxine to on-going neuroleptic treatment could improve minor depression in schizophrenic patients. METHOD: Nine schizophrenic patients with co-morbid minor depression participated in this study. All participants had a stable unchanged clinical state (changes in Brief Psychiatric Rating Scale (BPRS). Scale for the Assessment of Positive Symptoms (SAPS), and Scale for the Assessment of Negative symptoms (SANS) scores < 5%) and all were maintained on unchanged doses of anti-psychotic drugs for at least 4 consecutive weeks prior to initiation of the study. Participants received, open-label, pyridoxine 150 mg/day in addition to their anti-psychotic treatment for 4 consecutive weeks. Mental status was evaluated before, during, and at the end of 4 weeks of pyridoxine administration using the BPRS, SAPS, SANS and HAM-D. RESULTS: Two of the nine patients (22%), characterized by higher initial HAM-D and SANS scores, and by older age and longer duration of illness, experienced marked improvements in depressive symptoms (23% and 28% decrease in HAM-D scores) following 4 weeks of pyridoxine administration. In one of these two, the improvement in depressive symptoms was accompanied by a parallel decrease in SANS Scores. CONCLUSION: A subgroup of schizophrenic patients with comorbid minor depression may benefit from pyridoxine addition to their on-going anti-psychotic treatment.

Am J Epidemiol. 2001 Apr 1;153(7):688-94. Association of the B-vitamins pyridoxal 5'-phosphate (B(6)), B(12), and folate with lung cancer risk in older men.

Hartman TJ, Woodson K, Stolzenberg-Solomon R, Virtamo J, Selhub J, Barrett MJ, Albanes D.

Department of Nutrition, The Pennsylvania State University, University Park, PA, USA.

A nested case-control study was conducted within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort to test for associations between selected B-vitamins (folate, vitamin B(6), vitamin B(12)) and incident lung cancer. This trial was conducted in Finland between 1985 and 1993. Serum was analyzed for these nutrients and homocysteine among 300 lung cancer cases and matched controls (1:1). Odds ratios and 95% confidence intervals were determined in conditional and unconditional (controlling for the matching factors) logistic regression models, after adjusting for body mass index, years of smoking, and number of cigarettes smoked per day. No significant associations were seen between serum folate, vitamin B(12), or homocysteine and lung cancer risk. The authors found significantly lower risk of lung cancer among men who had higher serum vitamin B(6) levels. Compared with men with the lowest vitamin B(6) concentration, men in the fifth quintile had about one half of the risk of lung cancer (odds ratio = 0.51; 95% confidence interval: 0.23, 0.93; p-trend = 0.02). Adjusting for any of the other serum factors (folate, B(12), and homocysteine) either alone or jointly did not significantly alter these estimates. This is the first report from a prospectively conducted study to suggest a role for vitamin B(6) in lung cancer.

J Ren Nutr. 2001 Apr;11(2):67-72. Homocysteine lowering effect of different multivitamin preparations in patients with end-stage renal disease.

Dierkes J, Domrose U, Bosselmann KP, Neumann KH, Luley C.

Institute of Clinical Chemistry and Biochemistry, Magdeburg, Germany.

OBJECTIVE: Hyperhomocysteinemia occurs in nearly 100% of patients with end-stage renal disease (ESRD) and is associated with increased morbidity and mortality. Means to reduce elevated homocysteine concentrations is supplementation with folic acid, vitamin B6, and vitamin B12. However, doses of vitamins required for optimized treatment are subject of debate. Therefore, the effect of 2 different multivitamin preparations on the homocysteine concentrations in patients with ESRD were compared. DESIGN: Patients received 3 times per week either 2 tablets of preparation A (800 microg folic acid, 6 microg vitamin B12, 10 mg vitamin B6), 2 tablets of preparation B (160 microg folic acid, no vitamin B12, 10 mg vitamin B6), or placebo for a period of 12 weeks with control of total homocysteine (tHcy) levels at baseline, and at 4, 8, and 12 weeks. SETTING: The study was performed at the University Hospital of Magdeburg, Germany in patients with ESRD treated with chronic intermittent maintenance hemodialysis. RESULTS: Preparation A reduced the tHcy concentration significantly by nearly 50%, whereas preparation B did not change the tHcy concentration in comparison with placebo. However, tHcy was not normalized in the majority of patients receiving preparation A. CONCLUSION: The reduction of tHcy achieved by a multivitamin containing 800 microg folic acid was substantial and even higher than the reduction reported in supplementation studies using higher doses of folic acid alone. Nevertheless, hyperhomocysteinemia in ESRD patients appears relatively refractory to vitamin supplementation, in contrast with results obtained in healthy volunteers.

Wiad Lek. 2001;54(1-2):11-8.

[Evaluation of vitamin B6 and calcium pantothenate effectiveness on hair growth from clinical and trichographic aspects for treatment of diffuse alopecia in women]

[Article in Polish]

Brzezinska-Wcislo L.

Katedry i Kliniki Dermatologii Slaskiej Akademii Medycznej w Katowicach.

The aim of the study was the clinical and trichological examination (trichogram and hair loss evaluation) conducted comparatively before and after the treatment in 46 women between pubescence and 30 years of age who had symptoms of diffuse alopecia. Calcium pantothenate was administered twice a day orally in doses 100 mg for 4-5 months. Vitamin B6 was injected every day (i ampoule intramusculary) for the period of 20 to 30 days and repeated again after 6 month. On the basis of clinical and trichological studies it was revealed that vitamin B6 administered parenterally for a period of several weeks induces improvement in the hair condition in a number of women and it reduces the hair loss especially in alopecia of telogenic patomechanism. Whereas calcium pantothenate in feminine diffuse alopecia did not show clearly the positive effect.

Endocr Pract. 2000 Nov-Dec;6(6):435-41.

Hyperhomocysteinemia in type 2 diabetes mellitus: cardiovascular risk factors and effect of treatment with folic acid and pyridoxine.

Baliga BS, Reynolds T, Fink LM, Fonseca VA.

Department of Pathology, University of Arkansas for Medical Sciences and VA Medical Center, Little Rock, Arkansas, USA.

OBJECTIVE: To determine whether hyperhomocysteinemia (HH) exacerbates other cardiovascular risk factors and markers of coagulation and hemostasis in patients with type 2 diabetes mellitus (DM) and whether treatment of HH with vitamins will alter these risk factors. METHODS: We measured several cardiovascular risk factors and markers of coagulation and hemostasis in patients with type 2 DM with and without HH. We also treated patients with type 2 DM and coexistent HH with high doses of folic acid and pyridoxine to determine whether this treatment would lower plasma total homocysteine concentrations as well as correct other associated cardiovascular risk factors in this population. RESULTS: Plasma levels of plasminogen activator inhibitor type 1 and fibrinogen were significantly higher in all patients with DM in comparison with control subjects (P<0.01), whether they had HH or not. No significant difference was noted between the two groups of patients with DM. The presence of hypertension and microalbuminuria did not lead to a higher plasma total homocysteine. After treatment with folic acid, 15 mg daily, and pyridoxine, 600 mg daily, fasting (basal) plasma total homocysteine declined significantly in patients with DM from 12.3 +/- 2.9 micromol/L to 9.1 +/- 1.1 micromol/L (P<0.01). The peak post-methionine load plasma total homocysteine in the patients with DM decreased from 39.9 +/- 11.4 micromol/L to 30.4 +/- 6.5 micromol/L (P<0.05). Neither fasting nor peak plasma total homocysteine changed in normal subjects. None of the cardiovascular risk factors measured changed significantly with the vitamin treatment. CONCLUSION: The coexistence of type 2 DM and HH does not lead to an exacerbation of abnormalities in the measured variables of coagulation and hemostasis. Treatment with high doses of folic acid and pyridoxine lowers the plasma total homocysteine significantly but does not improve any of the associated cardiovascular risk factors that we measured. Long-term clinical trials should be conducted to determine whether high-dose vitamin treatment will diminish the increased morbidity and mortality associated with cardiovascular disease in patients with type 2 DM.

Nephrol Dial Transplant. 2000 Sep;15(9):1410-3. Vitamin B6 supplementation can improve peripheral polyneuropathy in patients with chronic renal failure on high-flux haemodialysis and human recombinant erythropoietin.

Okada H, Moriwaki K, Kanno Y, Sugahara S, Nakamoto H, Yoshizawa M, Suzuki H.

Department of Nephrology, Saitama Medical College, Irumagun, Saitama, Japan.

BACKGROUND: High-flux haemodialysis (HD) has recently been vigorously promoted as a novel standard, and it can indeed efficiently reduce the occurrence of most uraemic symptoms due to middle molecular toxins and/or underdialysis. However, some symptoms remain problematical, particularly peripheral polyneuropathy (PPN). One of the possible reasons for this is that the patients may have low concentrations of some nutrients, e.g. vitamin B(6), necessary for normal peripheral neuron function. METHODS: Predialysis serum pyridoxal-5'-phosphate (P5P) level was determined in 36 chronic HD patients who were undergoing high-flux HD and receiving human recombinant erythropoietin. Among them, 26 patients suffered from PPN. Prior to supplementation, these 26 patients were examined and their neurological symptoms were ranked according to our PPN symptom score. Vitamin B(6) (60 mg/day) was randomly prescribed to 14 of them, and vitamin B(12) (500 microg/day) was prescribed to the others. After 4 weeks, all the patients were re-examined. RESULTS: We found that predialysis serum P5P levels of HD patients with PPN were not significantly lower than those of matched HD patients without PPN. Nonetheless, it was demonstrated that supplementation with vitamin B(6) for 4 weeks significantly increased the predialysis level of P5P and dramatically attenuated PPN symptoms compared with initial symptoms. No improvement was observed in response to vitamin B(12) supplementation. CONCLUSION: This result suggests that although vitamin B(6) deficiency could not be demonstrated in patients with chronic renal failure on high-flux HD, vitamin B(6) supplementation was effective in improving PPN symptoms of various aetiologies, possibly because of vitamin B(6) resistance to PPN in these patients.

Pediatr Neurol. 2000 Sep;23(3):202-6. Long-term follow-up of vitamin B(6)-responsive West syndrome.

Ohtsuka Y, Ogino T, Asano T, Hattori J, Ohta H, Oka E.

Department of Child Neurology, Okayama University Medical School, Okayama, Japan.

We performed a clinical and electroencephalographic follow-up study on 25 patients with West syndrome that was responsive to vitamin B(6) (eight cryptogenic patients and 17 symptomatic patients) who were older than 3 years at the last follow-up. All cryptogenic patients and 13 symptomatic patients were seizure free at the last follow-up. All cryptogenic patients and seven symptomatic patients had intelligent quotient or developmental quotient scores of 75 or higher. The recurrence of clinical seizures was always associated with increases in epileptic discharges. We could successfully discontinue pyridoxal phosphate administration in four cryptogenic and four symptomatic patients who were 1 year, 8 months to 24 years old.

Crit Care Med. 2000 Jun;28(6):2116-8. Pyridoxine therapy in a patient with severe hydrazine sulfate toxicity.

Nagappan R, Riddell T.

Intensive Care Unit, Whangarei Hospital, New Zealand.

OBJECTIVE: To report hydrazine sulfate as a cause of severe encephalopathy and to report its response to high-dose pyridoxine therapy. DESIGN: Case report. SETTING: An adult six-bed medical/surgical intensive care unit of a general hospital. PATIENT: One patient who developed severe encephalopathy after hydrazine sulfate. INTERVENTION: 5 g i.v. pyridoxine. MEASUREMENTS AND MAIN RESULTS: After 180 mg/day for 2 wks followed by 360 mg/day of hydrazine sulfate ingestion, our patient suffered severe encephalopathy. He received mechanical ventilation with attendant supportive measures and high-dose pyridoxine. The patient's encephalopathy resolved 24 hrs after receiving pyridoxine. CONCLUSION: Severe encephalopathy could result from hydrazine sulfate toxicity. High-dose pyridoxine is an effective treatment to reverse this encephalopathy.

J Child Neurol. 2000 Jun;15(6):424-8.

Current therapy for West syndrome in Japan.

Ito M, Seki T, Takuma Y.

Department of Pediatrics, Shiga Medical Center for Children, Tokyo, Japan. m-ito@qa2.so-net.ne.jp

We sent questionnaires concerning the current therapy for West syndrome to 208 institutions at which pediatric care members of the Japan Epilepsy Society were working. Of these, 129 (62%) institutions responded. Vitamin B6 was the preferred first-line drug, followed by the combination of vitamin B6 and valproate or monotherapy with valproate. Corticotropin was the third choice among the drugs. The dosage of corticotropin was lower than previously reported. The treatment of West syndrome is not well established at present and further research is needed to improve the therapeutic protocol.

Med Hypotheses. 2000 May;54(5):808-13. Prenatal high-dose pyridoxine may prevent hypertension and syndrome X in-utero by protecting the fetus from excess glucocorticoid activity.

McCarty MF.

Pantox Laboratories, San Diego, California, USA.

The increased risk for hypertension, insulin resistance syndrome, and coronary events associated with small-for-gestational-age birth, has plausibly been attributed to excessive prenatal exposure to glucocorticoids; this may up-regulate glucocorticoid activity throughout life by permanently decreasing expression of hippocampal glucocorticoid receptors crucial for feedback control of cortisol secretion. Since pyridoxal phosphate is a safe physiological antagonist of glucocorticoid activity, it is proposed that prenatal supplementation with high-dose pyridoxine may counteract the adverse impact of glucocorticoids on fetal growth, as well as on subsequent cardiovascular risk. Copyright 2000 Harcourt Publishers Ltd.

Med Hypotheses. 2000 May;54(5):803-7. High-dose pyridoxine as an 'anti-stress' strategy.

McCarty MF.

Pantox Laboratories, San Diego, California, USA.

Pyridoxine nutritional status has a significant and selective modulatory impact on central production of both serotonin and GABA - neurotransmitters which control depression, pain perception, and anxiety - owing to the fact that the decarboxylases which produce these neurotransmitters have a relatively low affinity for pyridoxal phosphate (PLP). Pyridoxine deficiency leads to increased sympathetic outflow and hypertension in rodents, possibly reflecting decreased central production of these neurotransmitters; conversely, supplemental pyridoxine lowers blood pressure in many animal models of hypertension, and there is preliminary evidence for antihypertensive activity in humans as well. Additionally, physiological levels of PLP interact with glucocorticoid receptors to down-regulate their activity. Thus, high-dose pyridoxine, by amplifying tissue levels of PLP, may be expected to have a favorable impact on certain dysphoric mental states, while diminishing sympathetic output and acting peripherally to blunt the physiological impact of corticosteroids. In light of growing evidence that chronic dysphoria, particularly when accompanied by hopelessness or cynicism, has a major negative impact on morbidity and mortality from a wide range of disorders, high intakes of pyridoxine may have the potential to improve prognosis in many individuals. With respect to cardiovascular health, reduction of homocysteine levels should contribute to this benefit. These predictions are consistent with recent epidemiology correlating plasma PLP levels with risk for vascular events and overall survival. Copyright 2000 Harcourt Publishers Ltd.

Neth J Med. 2000 Apr;56(4):138-46. Normohomocysteinaemia and vitamin-treated hyperhomocysteinaemia are associated with similar risks of cardiovascular events in patients with premature atherothrombotic cerebrovascular disease. A prospective cohort study.

Vermeulen EG, Rauwerda JA, Erix P, de Jong SC, Twisk JW, Jakobs C, Witjes RJ, Stehouwer CD.

Department of Surgery, Vascular Surgical Unit, University Hospital "Vrije Universiteit", PO Box 7057, 1007 MB, Amsterdam, The Netherlands. egj.vermeulen@azvu.nl

BACKGROUND: Mild hyperhomocysteinaemia (HHC) is associated with an increased risk of premature atherothrombotic cerebrovascular disease. We investigated the clinical efficacy with regard to the incidence of cardiovascular events of treatment of mild HHC with vitamin B(6) plus folic acid. METHODS: We studied 224 consecutive patients with clinically manifest atherothrombotic cerebrovascular disease with onset before the age of 56. Follow-up was obtained in 203 (90.6%) patients. At baseline, 52 (25.6%) were hyperhomocysteinaemic after methionine loading and started treatment with vitamin B(6) (250 mg) plus folic acid (5 mg); 151 (74.4%) were normohomocysteinaemic (reference group). RESULTS: During follow-up (median 57 months), 31 (20.5%) of the normo- and 11 (21.2%) of the hyperhomocysteinaemic patients had a new cardiovascular event. The crude incidence rate per person-year for any cardiovascular event was similar in both groups (0.043 [CI, 0.029-0.057] in the normo- vs. 0.045 [CI, 0.021-0. 069] in the hyperhomocysteinaemic group). Multivariate Cox-regression analyses showed that hypertension and cholesterol levels were associated with an increased risk of new cardiovascular events in the total group [relative risk [RR] (yes vs. no), 7.4 (3. 4-16.0) and RR (per 1 mmol/l), 1.9 (CI, 1.4-2.7)]. The adjusted RR for new cardiovascular events in the hyper- as compared to the normohomocysteinaemic patients was 0.96 (CI, 0.48-1.92). CONCLUSION: These data are consistent with a protective effect of treatment with vitamin B(6) plus folic acid in patients with premature atherothrombotic cerebrovascular disease and post-methionine HHC.

J Womens Health Gend Based Med. 2000 Mar;9(2):131-9. A synergistic effect of a daily supplement for 1 month of 200 mg magnesium plus 50 mg vitamin B6 for the relief of anxiety-related premenstrual symptoms: a randomized, double-blind, crossover study.

De Souza MC, Walker AF, Robinson PA, Bolland K.

Department of Food Science and Technology, The University of Reading, United Kingdom.

To investigate single and combined effects of daily dietary supplementation with 50 mg of vitamin B6 and 200 mg magnesium (as MgO) for one cycle for the relief of mild premenstrual symptoms, a randomized, double-blind, placebo-controlled, crossover design was used. Forty-four women with an average age of 32 years took part in the study. Each woman was randomly assigned, according to a Latin square design, to take consecutively all four of the following treatments daily for one menstrual cycle: (1) 200 mg Mg, (2) 50 mg vitamin B6, (3) 200 mg Mg + 50 mg vitamin B6 and (4) placebo. Throughout the study, each volunteer kept a daily record of symptoms using a 5-point ordinal scale in a menstrual diary of 30 symptoms. Symptoms were grouped into six categories: anxiety, craving, depression, hydration, other, and total. Urinary magnesium output for 24 hours was estimated using the Mg/creatinine concentration ratio. ANOVA showed no overall difference between individual treatments, but predefined treatment comparisons using factorial contrasts in ANOVA showed a significant effect of 200 mg/day Mg + 50 mg/day vitamin B6 on reducing anxiety-related premenstrual symptoms (nervous tension, mood swings, irritability, or anxiety) (p = 0.040). Urinary Mg output was not affected by treatment. A small synergistic effect of a daily dietary supplementation with a combination of Mg + vitamin B6 in the reduction of mild premenstrual anxiety-related symptoms was demonstrated during treatment of 44 women for one menstrual cycle. In view of the modest effect found, further studies are needed before making general recommendations for the treatment of premenstrual symptoms. The study indicated that absorption from MgO was poor and daily supplementation for longer than 1 month is necessary for tissue repletion.

Lancet. 2000 Feb 12;355(9203):517-22.

Comment in: • Lancet. 2000 Feb 12;355(9203):511-2. • Lancet. 2000 Jun 24;355(9222):2249; author reply 2250. Effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on progression of subclinical atherosclerosis: a randomised, placebo-controlled trial.

Vermeulen EG, Stehouwer CD, Twisk JW, van den Berg M, de Jong SC, Mackaay AJ, van Campen CM, Visser FC, Jakobs CA, Bulterjis EJ, Rauwerda JA.

Department of General Surgery, University Hospital and Institute for Cardiovascular Research Vrije Universiteit, Amsterdam, The Netherlands.

BACKGROUND: A high plasma homocysteine concentration is associated with increased risk of atherothrombotic disease. We investigated the effects of homocysteine-lowering treatment (folic acid plus vitamin B6) on markers of subclinical atherosclerosis among healthy siblings of patients with premature atherothrombotic disease. METHODS: We did a randomised, placebo-controlled trial among 158 healthy siblings of 167 patients with premature atherothrombotic disease. 80 were assigned placebo and 78 were assigned 5 mg folic acid and 250 mg vitamin B6 daily for 2 years. The primary endpoint was the development or progression of subclinical atherosclerosis as estimated from exercise electrocardiography, the ankle-brachial pressure index, and carotid and femoral ultrasonography. FINDINGS: Ten participants in the treatment group, and 14 in the placebo group dropped out. Vitamin treatment, compared with placebo, was associated with a decrease in fasting homocysteine concentration (from 14.7 to 7.4 micromol/L vs from 14.7 to 12.0 micromol/L), and in postmethionine homocysteine concentration (from 64.9 to 34.9 micromol/L vs from 64.8 to 50.3 micromol/L). It was also associated with a decreased rate of abnormal exercise electrocardiography tests (odds ratio 0.40 [0.17-0.93]; p=0.035). There was no apparent effect of vitamin treatment on ankle-brachial pressure indices (0.87 [0.56-1.33]), or on carotid and peripheral-arterial outcome variables (1.02 [0.26-4.05] and 0.86 [0.47-1.59], respectively). INTERPRETATION: Homocysteine-lowering treatment with folic acid plus vitamin B6 in healthy siblings of patients with premature atherothrombotic disease is associated with a decreased occurrence of abnormal exercise electrocardiography tests, which is consistent with a decreased risk of atherosclerotic coronary events.

Med Clin (Barc). 2000 Jan 15;114(1):7-12. [Lowering high levels of fasting total homocysteine with folic acid and vitamins B in patients with venous thromboembolism: relationship between response and the C677T methylenetetrahydrofolate reductase (MTHRF) genotype]

[Article in Spanish]

Gonzalez Ordonez AJ, Medina Rodriguez JM, Fernandez Alvarez CR, Sanchez Garcia J, Fernandez Carreira JM, Alvarez Martinez MV, Coto Garcia E.

Servicio de Hematologia, Hospital San Agustin, Aviles. jagonzalez@medynet.com

BACKGROUND: High levels of plasma total homocysteine (tHcy) are involved in arterial or venous occlusive diseases. It essentially depends on the nutritional status of folic acid (FA) and vitamins B12 or B6, but also on the methylenetetrahydrofolate reductase (MTHFR) enzymatic activity. We aim to evaluate the response of the hyperhomocysteinemia (HHcy) to a standard schedule of vitamin supplementation, according with the MTHFR genotype. PATIENTS AND METHODS: 227 patients, diagnosed with venous thromboembolism (VTE) were analysed for tHcy (in fasting conditions), and for the MTHFR-C677T gene polymorphism. When the tHcy exceeded the cut-off point (men = 16, women = 15 mumol/l), the patients were supplemented with a dose equivalent to 1 mg FA, 0.2 mg B12 and 100 mg of B6, daily by 6 weeks. Afterwards they were reanalysed and the reduction was stratified by MTHFR genotype, looking for any difference in the response. RESULTS: The mean fasting tHcy was 12.3 mumol/l (SD = 8). The 51 hyperhomocysteinemic patients (22%) were older (65.1 y) than the normal ones (55.0 y) (p = 0.0001). The treatment was carried out properly in 46 patients (90%). The pre-treatment mean Hcy was 23.2 (SD = 10.5) mumol/l, and it was reduced to 13.0 (SD = 5.9) (p = 0.0001) (mean reduction = 42.1%). By genotype, the C/C reduced from 21.0 to 13.2 mumol/l (37%) (n = 18), the C/T from 25.0 to 12.6 mumol/l (46%) (n = 24), and the abnormal homozygotes T/T from 22.7 to 14.5 mumol/l (39%) (n = 4), although no statistical significant differences were found. In 80% of cases (37/46), tHcy values normalised. A negative correlation (r = -0.471) (p = 0.005) was observed between age and response. CONCLUSIONS: The FA/B6/B12 based therapy reduces in a simple, quick and effective way (> 40% in 6 weeks) the pathologic tHcy levels on a VTE population and this is not influenced by the MTHFR genotype. As HHcy seems related with recurrences of venous thrombosis, we could speculate if it would be useful to analyse routinely the tHcy, attempting reduction in selected cases.

Arch Tierernahr. 2000;53(3):227-39.

Effects of vitamin B6 supplementation in rats during lactation on vitamin B6 concentration and transaminase activities in the offspring.

Roth-Maier DA, Kettler SI, Benedikt J, Kirchgessner M.

Institute of Nutritional Sciences, Technical University Munich, Freising-Weihenstephan, Germany. Roth-Maier@weihenstephan.de

The aim of the present investigation was to study the effect of a varying maternal vitamin B6 supplementation during lactation period on vitamin B6 levels in blood, liver and total body, and on the activity of two transaminase enzymes in the offspring. Therefore, eighty female Sprague-Dawley rats were fed a semi-synthetic diet (0.2 mg vitamin B6 per kg) which was supplemented during gravidity with 5 mg vitamin B6 per kg diet. During the following lactation period the rats were assigned to one of 10 vitamin B6 treatment groups (supplementation of 0, 3, 6, 9, 12, 15, 18, 36, 360, 3600 mg vitamin B6 per kg diet). At day 14 of lactation the pubs of all dams were decapitated and blood, liver, and carcass were used for analysis of vitamin B6 concentration, activities of two transaminases, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in plasma, erythrocytes, and liver, and of haematological parameters. While the liver and total body wet weights as well as the haematological parameters (red blood cells, haemoglobin concentration, hematocrit, middle corpuscular cell volume, middle corpuscular haemoglobin, middle corpuscular haemoglobin concentration) did not differ within the experimental groups, the present data clearly show that in blood, liver and total body of the offspring exists a slight dose-response relationship between the maternal dietary vitamin B6 supplementation and the vitamin B6 concentration. Concerning the activities of the transaminases a dietary supplementation above 3 mg vitamin B6 per kg diet had no influence on the AST and ALT activities in offspring plasma. In the erythrocytes no statistical significant influence of the vitamin B6 supplementation during lactation on the activities of AST and ALT was found. The activities of ALT and AST in liver were not consistently altered by the vitamin B6 supplementation of the dams during lactation. In conclusion these results indicate that a minimal maternal dietary vitamin B6 supply of 3.1 mg per kg diet is necessary with regard to health and development of their offspring. But not all of the analysed parameters as the liver and total body weights, the activities of AST and ALT in the erythrocytes, and the haematological parameters were influenced by a deficient maternal dietary vitamin B6 supply.

J Anim Sci. 2000 Jan;78(1):88-93. Added dietary pyridoxine, but not thiamin, improves weanling pig growth performance.

Woodworth JC, Goodband RD, Nelssen JL, Tokach MD, Musser RE.

Department of Animal Sciences and Industry, Kansas State University, Manhattan 66506-0210, USA.

We conducted two trials to determine the effects of added dietary pyridoxine (vitamin B6) or thiamin (vitamin B1) on growth performance of weanling pigs. In Exp. 1, weanling pigs (n = 180, initially 5.55 +/- .84 kg, and 21 +/- 2 d of age) were fed either a control diet (no added pyridoxine or thiamin) or the control diet with added thiamin (2.8 or 5.5 mg/kg) from thiamin mononitrate or pyridoxine (3.9 or 7.7 mg/kg) from pyridoxine HC1. These five diets were fed in meal form in two phases (d0 to 14 and 14 to 35 after weaning), with identical vitamin concentrations in both phases. From d 0 to 14 after weaning, pigs fed added pyridoxine had increased (quadratic, P < .05) ADG and ADFI; pigs fed 3.9 mg/kg of added pyridoxine had the greatest improvement. From d 14 to 35 and 0 to 35, ADG and ADFI increased (linear P = .06) for pigs fed increasing pyridoxine. Growth performance was not improved by added thiamin. In Exp. 2, weanling pigs (n = 216, initially 6.08 +/- 1.13 kg, and 21 +/- 2 d of age) were fed a control diet or the control diet with 1.1, 2.2, 3.3, 4.4, or 5.5 mg/kg of added pyridoxine from pyridoxine HCl. From d 0 to 14 after weaning, increasing pyridoxine increased (quadratic, P < .05) ADG and ADFI; pigs fed 3.3 mg/kg of added pyridoxine had the greatest ADG and ADFI. Break-point analysis suggested a requirement estimate of 3.3 and 3.0 mg/kg of added pyridoxine to maximize ADG and ADFI, respectively. From d 14 to 35 or 0 to 35, increasing pyridoxine had no effect (P > .10) on pig growth performance. These results suggest that adding 3.3 mg/kg of pyridoxine (7.1 to 7.9 mg/kg of total pyridoxine) to diets fed from d 0 to 14 after weaning can improve pig growth performance.

Am J Cardiol. 1999 Dec 1;84(11):1359-61, A8. Effect of short-term vitamin (folic acid, vitamins B6 and B12) administration on endothelial dysfunction induced by post-methionine load hyperhomocysteinemia.

Chao CL, Chien KL, Lee YT.

Department of Internal Medicine (Cardiology), National Taiwan University Hospital, Taipei. clchao@ha.mc.ntu.edu.tw

This study showed that short-term vitamin administration effectively reduced post-methionine load homocysteine levels and thereby ameliorated endothelium-dependent flow-mediated vasodilation in 16 healthy adults. Post-methionine load homocysteine levels decreased from 22.7+/-3.8 to 17.0+/-2.1 micromol/L (p <0.001), and flow-mediated vasodilation after methionine load increased from 8.6+/-3.6% to 13.8+/-2.9% (p <0.001) after vitamin administration.

Kidney Int. 1999 Dec;56(6):2292-6. Effective correction of hyperhomocysteinemia in hemodialysis patients by intravenous folinic acid and pyridoxine therapy.

Touam M, Zingraff J, Jungers P, Chadefaux-Vekemans B, Drueke T, Massy ZA.

Division of Nephrology, INSERM U507, and Biochemistry B Laboratory, Necker Hospital, Paris, France.

Effective correction of hyperhomocysteinemia in hemodialysis patients by intravenous folinic acid and pyridoxine therapy. BACKGROUND: Folic acid supplementation is only partially efficacious in correcting moderate elevation of plasma total homocysteine (tHcy) concentrations observed in hemodialysis (HD) patients. Experimental and clinical data have suggested that this partial efficacy may be due to impairment of folic acid metabolism to 5-methyltetrahydrofolate (MTHF) and of MTHF transmembrane transport as well. To bypass these difficulties, we assessed the efficacy of intravenous (i.v.) folinic acid, a ready precursor of MTHF, on reducing plasma tHcy concentrations in HD patients. METHODS: In a cohort of 37 patients on intermittent HD treatment, plasma tHcy concentrations were determined before and during i.v. supplementation of folinic acid (50 mg once per week), together with i.v. pyridoxine (250 mg 3 times per week), to prevent vitamin deficiency, particularly in those treated by recombinant erythropoietin. RESULTS: Folinic acid and pyridoxine i.v. supplementation was given for 11.2 +/- 2.45 months (range 7.5 to 17 months). The mean plasma tHcy levels decreased significantly from 37. 3 +/- 5.8 microM at baseline to 12.3 +/- 5.4 microM on folinic acid treatment (P < 0.001). Moreover, 29 of the 37 patients (78%) had normal plasma tHcy levels at the end of follow-up (that is, <14.1 microM, mean 9.8 microM, range 6.2 to 13 microM). No adverse effects attributable to folinic acid treatment were observed during this time. CONCLUSIONS: Intravenous folinic acid therapy (50 mg) once per week associated with pyridoxine supplementation appears to be an effective and safe strategy to normalize plasma tHcy levels in the majority of chronic HD patients.

Am J Clin Nutr. 1999 Nov;70(5):881-7. Increased dietary micronutrients decrease serum homocysteine concentrations in patients at high risk of cardiovascular disease.

Chait A, Malinow MR, Nevin DN, Morris CD, Eastgard RL, Kris-Etherton P, Pi-Sunyer FX, Oparil S, Resnick LM, Stern JS, Haynes RB, Hatton DC, Metz JA, Clark S, McMahon M, Holcomb S, Reusser ME, Snyder GW, McCarron DA.

Division of Metabolism, Department of Medicine, University of Washington, Seattle, USA.

BACKGROUND: Elevated blood homocysteine is a risk factor for cardiovascular disease. A 5-micromol/L increase is associated with an approximately 70% increase in relative risk of cardiovascular disease in adults. For patients with established risk factors, this risk is likely even greater. OBJECTIVE: Effects of increased dietary folate and recommended intakes of vitamins B-12 and B-6 on serum total homocysteine (tHcy) were assessed in individuals at high risk of cardiovascular disease. DESIGN: This trial was conducted at 10 medical research centers in the United States and Canada and included 491 adults with hypertension, dyslipidemia, type 2 diabetes, or a combination thereof. Participants were randomly assigned to follow a prepared meal plan (PMP; n = 244) or a self-selected diet (SSD; n = 247) for 10 wk, which were matched for macronutrient content. The PMP was fortified to provide >/=100% of the recommended dietary allowances for 23 micronutrients, including folate. RESULTS: Mean folate intakes at 10 wk were 601 +/- 143 microgram/d with the PMP and 270 +/- 107 microgram/d with the SSD. With the PMP, serum tHcy concentrations fell from 10.8 +/- 5.8 to 9.3 +/- 4.9 micromol/L (P < 0.0001) between weeks 0 and 10 and the change was associated with increased intakes of folate, vitamin B-12, and vitamin B-6 and with increased serum and red blood cell folate and serum vitamin B-12 concentrations. tHcy concentrations did not change significantly with the SSD. CONCLUSIONS: The PMP resulted in increased intakes and serum concentrations of folate and vitamin B-12. These changes were associated with reduced serum tHcy concentrations in persons at high risk of cardiovascular disease.

Arch Dis Child. 1999 Nov;81(5):431-3. Epidemiology of pyridoxine dependent and pyridoxine responsive seizures in the UK.

Baxter P.

Ryegate Centre, Sheffield Children's Hospital, Tapton Crescent, Sheffield S10 5DD, UK. p.s.baxter@sheffield.ac.uk

OBJECTIVE: To study the epidemiology of pyridoxine dependent seizures and other forms of pyridoxine responsive seizures. DESIGN: Monthly notifications to the British Paediatric Surveillance Unit over two years. Questionnaire follow up. SETTING: UK and the Republic of Ireland. PATIENTS: Children aged 15 years or younger whose seizures respond to pyridoxine. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Numbers of children with definite, probable, and possible pyridoxine dependent seizures or other seizures responsive to pyridoxine. RESULTS: Point prevalence and birth incidence: 1/687 000 and 1/783 000, respectively (definite and probable cases); 1/317 000 and 1/157 000, respectively (all types of pyridoxine responsiveness). NOTIFICATIONS: Pyridoxine dependency: 14 definite, 9 probable, and 10 possible cases; neonatal seizures not meeting case definitions: 7; infantile spasms: 5. Eight of 18 families of definite/probable cases had 2 affected siblings. Just over a third had atypical presentations and just under a third had features and/or initial diagnoses of birth asphyxia and neonatal hypoxic ischaemic encephalopathy. CONCLUSIONS: Pyridoxine dependency is rare. Atypical presentations are relatively frequent. A trial of pyridoxine is justified in all cases of early onset intractable seizures or status epilepticus, whatever the suspected cause.

Med Pregl. 1999 Nov-Dec;52(11-12):501-4.

[A case report of pyridoxine-responsive homocystinuria]

[Article in Croatian]

Milosevic-Tosic M, Borota J, Katanic D, Vlaski J.

Institut medicinskih sluzbi, Zavod za biohemiju, Medicinski fakultet, Novi Sad.

INTRODUCTION: Homocystinuria is a rare, congenital, autosomal-recessive, metabolic disease biochemically characterized by homocysteinemia and homocystinuria and by multi-system clinical disorders. It is a biochemical abnormality of methionine metabolism caused either by transulfuration pathway disorders or by disorders of homocysteine remethilation into methionine and as such it can be a result of numerous specific and different genetic lesions. CASE REPORT: Homocystinuria is most commonly caused by deficiency of cystationine beta synthetase enzyme which catalyses the synthesis of cystathionine from homocysteine and serine in the methinione pathway. This results in accumulation of homocysteine and methionine in plasma and leads to excretion of excessive urinary homocysteine. Depending on specific property of the mutant enzyme molecule some patients respond to very high doses of pyridoxine with decreases of methionine and homocystine and some not. Pyridoxine responsiveness is based on the presence of small residual activity of cystathionine beta synthetase which is not present in nonresponsive patients. Homocystinuria due to cystathionine beta-synthase (CBS) deficiency is characterized by numerous different clinical abnormalities, but changes in four organ systems are dominant (eye, skeletal, central nervous and vascular system). CASE DESCRIPTION: Six years ago a six year-old boy was admitted to the hospital with vision problems. Ophthalmologic examination revealed a lens dislocation and because of many stigmates the child was sent to endocrinologist. The child had a marfanoid stature, with pectus carinatum and genu valgum, ataxic gait with motoric discoordination, muscle tone which ranged from hypotonia to hypertonia of extrapvramidal type and low intellectual abilities. A simple cyanide-nitroprusside test of patient's urine was positive suggesting homocystinuria. The diagnosis was established after plasma and urine amino acid analysis by HPLC. Concentration of homocystine and methionine were 52 mumol/l and 57 mumol/l in plasma and 249 mumol/du and 55 mumol/du in urine, respectively. After four months of treatment with pyridoxine there were not any significant changes in plasma homocysteine and methionine, but at the same time decrease in urine of these two amino acids were more than 2.5 times higher. This confirms that the patient has a pyridoxine-responsive type of homocystinuria and the dose was increased to 60 mg/day and 600 mg/day. This results in further decline of homocysteine and methionine in plasma and urine which persists up to now (for six years).

J Child Neurol. 1999 Oct;14(10):687-90.

Pyridoxine-dependent seizures in an older child.

Yoshikawa H, Abe T, Oda Y.

Department of Pediatrics, Niigata City General Hospital, Niigata, Japan. yos@seagreen.ocn.ne.jp

The case of a 12-year-old girl with pyridoxine-dependent seizures is reported. She developed status epilepticus just after birth and ordinary antiepileptic drugs were administered without effect. Her seizures ceased only on the administration of pyridoxine. Status epilepticus associated with the withdrawal of pyridoxine occurred three times, and ceased only after the renewed administration of pyridoxine. She now has mental retardation and mild spastic diplegia. The reported cases of pyridoxine-dependent seizures usually have been neonates and infants. Older patients were not fully investigated, and so we have reviewed these cases of pyridoxine-dependent seizures. As known previously, pediatricians should not forget that pyridoxine should be continued for life.

Mol Cell Biochem. 1999 Oct;200(1-2):155-62.

Dietary vitamin B6 supplementation attenuates hypertension in spontaneously hypertensive rats.

Vasdev S, Ford CA, Parai S, Longerich L, Gadag V.

Department of Medicine, Health Sciences Centre, Memorial University of Newfoundland, St. John's, Canada.

In spontaneously hypertensive rats (SHRs) excess endogenous aldehydes bind sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels, increasing cytosolic free calcium and blood pressure. N-acetyl cysteine normalizes elevated blood pressure in SHRs by binding excess endogenous aldehydes. It is known that dietary vitamin B6 supplementation can increase the level of endogenous cysteine. Our objective was to investigate whether a dietary supplementation of vitamin B6 can prevent hypertension and associated changes in SHRs. Starting at 7 weeks of age, animals were divided into three groups of six animals each. Animals in WKY-control group and SHR-control group were given a normal vitamin B6 diet; and SHR-vitamin B6 group, a high vitamin B6 diet (20 times the recommended dietary intake; RDA) for the next 14 weeks. After 14 weeks, systolic blood pressure, platelet [Ca2+]i and liver, kidney and aortic aldehyde conjugates were significantly higher in SHR controls compared to WKY controls. These animals also showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. Dietary vitamin B6 supplementation attenuated the increase in systolic blood pressure, tissue aldehyde conjugates and associated changes. These results further support the hypothesis that aldehydes are involved in increased systolic blood pressure in SHRs and suggest that vitamin B6 supplementation may be an effective antihypertensive.

Thromb Res. 1999 Sep 15;95(6):281-8. Treatment of hyperhomocysteinemia with folic acid and vitamins B12 and B6 attenuates thrombin generation.

Undas A, Domagala TB, Jankowski M, Szczeklik A.

Department of Medicine, University School of Medicine, Cracow, Poland.

The effect of homocysteine-lowering treatment on thrombin generation was investigated in 17 subjects with hyperhomocysteinemia (aged 22-60 years), 11 of whom had symptomatic atherosclerotic vascular disease. All subjects had fasting total homocysteine levels above 16 micromol/L. The formation of thrombin was assessed by measuring thrombin-antithrombin III complexes and prothrombin fragment 1+2 in peripheral venous blood and in the bleeding time blood collected at 30-second intervals from skin incisions on a forearm. All the tests were performed before and after an 8-week treatment with folic acid p.o. 5 mg/day, vitamin B6 p.o. 300 mg/day, and vitamin B12 i.m. 1000 microg given on a weekly basis. Following the 8-week therapy, the median plasma homocysteine concentration became significantly reduced from 20 to 10 micromol/L, while plasma levels of fibrinogen, prothrombin, and antithrombin III as well as activity of protein C, S, and factor VII showed no changes. Vitamin treatment was associated with a significant fall in thrombin-antithrombin III complexes and prothrombin fragment 1+2 concentrations in peripheral venous blood. Bleeding time became prolonged by about 60 seconds. At sites of hemostatic plug formation, plasma concentrations of both thrombin markers significantly decreased. Compared with pretreatment values, significantly less thrombin was produced during the first 3 minutes of bleeding after homocysteine-lowering therapy. In subjects with hyperhomocysteinemia a reduction of plasma fasting homocysteine concentration by folic acid and vitamins B12 and B6 administration is associated with attenuation of thrombin generation both in peripheral blood and at sites of hemostatic plug formation.

J Nutr Sci Vitaminol (Tokyo). 1999 Aug;45(4):449-58.

Adequacy of maternal pyridoxine supplementation during pregnancy in relation to the vitamin B6 status and growth of neonates at birth.

Chang SJ.

Department of Biology, National Cheng Kung University, Tainan, Taiwan. sjchang@mail.ncku.edu.tw

To evaluate the adequacy of maternal pyridoxine supplementation during pregnancy for both maternal and neonatal status at birth, vitamin B6 status, assessed by plasma pyridoxal phosphate (PLP), pyridoxal (PL) and total aldehyde vitamer (PLP + PL) concentrations, and the growth of neonates, including weight, length, head and chest circumferences, were examined for 209 neonates whose mothers were supplemented with 0, 1, 2 or 3 mg pyridoxine.HCl (PN.HCl)/d during pregnancy. Maternal PN.HCl supplementations were positively correlated to both maternal (r = 0.62) and cord (r = 0.78) plasma PLP concentrations (p < 0.0001). Mothers supplemented with 2 or 3 mg/d PN.HCl had significantly higher plasma concentrations of PLP and total B6 aldehyde vitamer in maternal and cord blood compared with those receiving 0 or 1 mg PN.HCl/d. A growth benefit for neonates whose mothers had maternal and cord plasma PLP concentrations > or = 40 nM was revealed by the maternal supplementation of 2 mg PN.HCl/d during pregnancy. Thus, in healthy pregnant women, according to our study, a daily supplement of 2 mg PN.HCl provides the adequacy of maternal and neonatal vitamin B6 status and the satisfactory growth of neonates at birth.

Rinsho Ketsueki. 1999 Aug;40(8):667-72.

[An infant case of sideroblastic anemia that responded to oral pyridoxine]

[Article in Japanese]

Kudo K, Ito M, Horibe K, Iwase K, Kojima S.

Department of Pediatrics, Nagoya University School of Medicine.

An 8-month-old boy was admitted because of paleness. Laboratory studies disclosed microcytic and hypochromic anemia: red blood cell count 156 x 10(4)/microliter, hemoglobin 3.5 g/dl, mean cell volume 66 fl, and reticulocytes 0.5/1000. Serum iron was 433 micrograms/dl and exocrine pancreatic dysfunction was not observed. Examination of bone marrow revealed prominent erythroid hyperplasia; 18% of the erythroblasts were distinct ringed sideroblasts. Electron microscopic studies found intramitochondrial iron deposits in the erythroblasts. The patient was given a diagnosis of sideroblastic anemia and responded to oral pyridoxine (50 mg/day) with an immediate increase of reticulocytes to 97/1000, resulting in an improved hemoglobin concentration. He has maintained remission for more than 1 year following discontinuation of pyridoxine, which was administered for 2 months. Congenital sideroblastic anemia is relatively rare and mostly occurs in males, suggesting an X-linked recessive mode of inheritance. Recently, X-linked sideroblastic anemia has been shown to be caused by missense mutations in the delta-aminolevulinic acid synthase (ALAS) gene. A point mutation in exon 5 of the ALAS gene was found in this patient. Iron-deficiency anemia is the most common hematologic disease of infancy and childhood, resulting from lack of sufficient iron for synthesis of hemoglobin. It is therefore mandatory to differentiate sideroblastic anemia from iron-deficiency anemia and other common anemias.

Clin Neuropharmacol. 1999 Jul-Aug;22(4):241-3.

Vitamin B6 in treatment of tardive dyskinesia: a preliminary case series study.

Lerner V, Kaptsan A, Miodownik C, Kotler M.

Ministry of Health Mental Health Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

Tardive dyskinesia (TD) remains a significant problem for patients and physicians. Several reports have suggested that vitamin B6 (pyridoxine) can be helpful in the treatment of some neuroleptic-induced movement disorders, including parkinsonism and TD. This report presents the results of a preliminary study of five patients with TD who underwent a four week open-label clinical trial of vitamin B6 (100 mg/d) in addition to their regular medications. The severity of the involuntary movements was assessed using the Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS) and the Simpson-Angus Scale (SAS). The patients' clinical status was assessed with the Brief Psychiatric Rating Scale (BPRS). With the addition of vitamin B6 to their treatment, four patients had clinically significant (greater than 30%) improvement on the measures of involuntary movement and, in three cases, there was also clinically significant improvement on the BPRS. None of the patients had side effects attributable to vitamin B6. The results suggest that vitamin B6 may alleviate TD, but it will need to be further tested in controlled double-blind trials.

J Intern Med. 1999 Jul;246(1):87-96. Normohomocysteinaemia and vitamin-treated hyperhomocysteinaemia are associated with similar risks of cardiovascular events in patients with premature peripheral arterial occlusive disease. A prospective cohort study.

de Jong SC, Stehouwer CD, van den Berg M, Geurts TW, Bouter LM, Rauwerda JA.

Institute for Cardiovascular Research, Vrije Universiteit, Amsterdam, The Netherlands.

OBJECTIVES: Mild hyperhomocysteinaemia (HHC), fasting or after methionine loading, is associated with an increased risk and severity of atherosclerotic vascular disease. Post-methionine and fasting HHC are responsive to treatment with vitamin B, and folic acid. We performed a prospective cohort study amongst normohomocysteinaemic and vitamin-treated (vitamin B6, 250 mg plus folic acid, 5 mg daily) hyperhomocysteinaemic patients with premature peripheral arterial occlusive disease and assessed the incidence of cardiovascular events. DESIGN: We studied 273 consecutive patients with clinically manifest peripheral arterial occlusive disease with onset before the age of 56, 79 (28.9%) of whom had postmethionine HHC. Follow-up was obtained in 232 (85'%o) patients. At baseline, 70 (30')/) were hyperhomocysteinaemic after methionine loading and started treatment with vitamin B, and folic acid; 162 (70%) were normohomocysteinaemic (reference group). RESULTS: During the follow-up period (median 20, range 1-63 months), 48 (29.6%) and 23 (32.9%) of the normo- and the hyperhomocysteinaemic patients, respectively, had a new cardiovascular event. Most (75%) involved the peripheral arterial system. The crude incidence rate for any cardiovascular event was 0.16 (95% CI, 0.12-0.21) per person per year in the normohomocysteinaemic and 0.16 (95% CI, 0.09-0.22) per person per year in the hyperhomocysteinaemic group. Multivariate Cox regression analyses showed that higher plasma homocysteine levels were associated with an increased risk of new cardiovascular events in the normohomocysteinaemic patients (relative risk [RR] per 1 micromol L(-1), 1.17 [CI, 1.05-1.30] for fasting and 1.06 [CI, 1.01-1.12] for postmethionine levels), but not in the hyperhomocysteinaemic (vitamin-treated) patients. The adjusted RR for new cardiovascular events in the hyper- as compared to the normohomocysteinaemic patients was 0.76 (CI, 0.33-1.74). CONCLUSIONS: These data are consistent with a protective effect of treatment with vitamin B6 and folic acid in patients with premature peripheral arterial occlusive disease and postmethionine HHC. Double-blind randomized trials are necessary to confirm this.

Cancer Epidemiol Biomarkers Prev. 1999 Jun;8(6):513-8. Methylenetetrahydrofolate reductase, diet, and risk of colon cancer.

Slattery ML, Potter JD, Samowitz W, Schaffer D, Leppert M.

University of Utah Medical School, Salt Lake City 84108, USA.

Individuals with different forms of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, carriers of the C677T mutation versus wild type, show differences in enzyme levels; these differences have been hypothesized to be related to DNA methylation and, perhaps, to the nucleotide pool size. Using data from an incident case-control study, we evaluated the combined effect of dietary intake of folate, methionine, vitamin B6, vitamin B12, and alcohol and various forms of the MTHFR gene on risk of colon cancer. Individuals homozygous for the variant form of the MTHFR gene (TT) had a slightly lower risk of colon cancer than did individuals who were wild type [CC, odds ratio (OR) = 0.8, 95% confidence interval (CI) = 0.6-1.1 for men; and OR = 0.9, 95% CI = 0.6-1.2 for women]. High levels of intake of folate, vitamin B6, and vitamin B12 were associated with a 30-40% reduction in risk of colon cancer among those with the TT relative to those with low levels of intake who were CC genotype. Associations were stronger for proximal tumors, in which high levels of intake of these nutrients were associated with a halving of risk among those with the TT genotype. The inverse association with high levels of these nutrients in those with the TT genotype was stronger among those diagnosed at an older age. Although imprecise, the inverse association with the low-risk diet that was high in folate and methionine and without alcohol was observed for both the TT genotype (OR = 0.4 95% CI = 0.1-0.9) and the CC/CT genotype (OR = 0.6, 95% CI = 0.4-1.0), but this association was not seen with the high-risk diet for either the TT or CC/CT genotype. Although associations were generally weak, these findings suggest that those with differing MTHFR genotypes may have different susceptibilities to colon cancer, based on dietary consumption of folate, vitamin B6, and vitamin B12.

J Am Soc Nephrol. 1999 Jun;10(6):1287-96. Effects of high-dose folic acid and pyridoxine on plasma and erythrocyte sulfur amino acids in hemodialysis patients.

Suliman ME, Divino Filho JC, Barany P, Anderstam B, Lindholm B, Bergstrom J.

Department of Clinical Science, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden.

In this investigation, sulfur amino acids (sAA) and sulfhydryls were determined in the plasma and erythrocytes (RBC) of 10 uremic patients on regular hemodialysis (HD) treatment and 10 healthy subjects, before and after supplementation with 15 mg/d of folic acid and 200 mg/d of pyridoxine for 4 wk. The basal total plasma concentrations of homocysteine (Hcy), cysteine (Cys), cysteinylglycine (Cys-Gly), gamma-glutamylcysteine (gamma-Glu-Cys), glutathione (GSH), and free cysteinesulfinic acid (CSA) were significantly higher in HD patients when compared to healthy subjects, whereas methionine (Met) and taurine (Tau) concentrations were the same in the two groups. HD patients showed significantly higher RBC levels of Hcy and Cys-Gly, whereas the RBC concentrations of Met, Cys, Tau, and GSH were not different from those in the healthy subjects. The plasma concentrations of sAA and sulfhydryls differed compared with RBC levels in the healthy subjects and HD patients. In both groups, supplementation with high doses of folic acid and pyridoxine reduced the plasma Hcy concentration. In addition, increased plasma concentrations of Cys-Gly and GSH were found in the HD patients and of CSA in the healthy subjects. After vitamin supplementation, the RBC concentrations of Hcy, Cys, and GSH increased and that of Tau decreased in healthy subjects. The only significant finding in RBC of HD patients was an increase in GSH levels after supplementation. This study shows several RBC and plasma sAA and sulfhydryl abnormalities in HD patients, which confirms earlier findings that RBC and plasma pools play independent roles in interorgan amino acid transport and metabolism. Moreover, high-dose supplementation with folic acid and pyridoxine significantly reduced Hcy levels, but did not restore the sAA and sulfhydryl abnormalities to normal levels. The increase that was observed in GSH after vitamin supplementation may have a beneficial effect in improving blood antioxidant status in uremic patients. Finally, the findings of elevated plasma Cys levels correlating to the elevated plasma Hcy levels in the presence of elevated plasma CSA levels, both before and after vitamin supplementation, led to the hypothesis that a block in decarboxylation of CSA is linked to hyperhomocysteinemia in end-stage renal failure.

J Am Soc Nephrol. 1999 Jun;10(6):1287-96. Effects of high-dose folic acid and pyridoxine on plasma and erythrocyte sulfur amino acids in hemodialysis patients.

Suliman ME, Divino Filho JC, Barany P, Anderstam B, Lindholm B, Bergstrom J.

Department of Clinical Science, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden.

In this investigation, sulfur amino acids (sAA) and sulfhydryls were determined in the plasma and erythrocytes (RBC) of 10 uremic patients on regular hemodialysis (HD) treatment and 10 healthy subjects, before and after supplementation with 15 mg/d of folic acid and 200 mg/d of pyridoxine for 4 wk. The basal total plasma concentrations of homocysteine (Hcy), cysteine (Cys), cysteinylglycine (Cys-Gly), gamma-glutamylcysteine (gamma-Glu-Cys), glutathione (GSH), and free cysteinesulfinic acid (CSA) were significantly higher in HD patients when compared to healthy subjects, whereas methionine (Met) and taurine (Tau) concentrations were the same in the two groups. HD patients showed significantly higher RBC levels of Hcy and Cys-Gly, whereas the RBC concentrations of Met, Cys, Tau, and GSH were not different from those in the healthy subjects. The plasma concentrations of sAA and sulfhydryls differed compared with RBC levels in the healthy subjects and HD patients. In both groups, supplementation with high doses of folic acid and pyridoxine reduced the plasma Hcy concentration. In addition, increased plasma concentrations of Cys-Gly and GSH were found in the HD patients and of CSA in the healthy subjects. After vitamin supplementation, the RBC concentrations of Hcy, Cys, and GSH increased and that of Tau decreased in healthy subjects. The only significant finding in RBC of HD patients was an increase in GSH levels after supplementation. This study shows several RBC and plasma sAA and sulfhydryl abnormalities in HD patients, which confirms earlier findings that RBC and plasma pools play independent roles in interorgan amino acid transport and metabolism. Moreover, high-dose supplementation with folic acid and pyridoxine significantly reduced Hcy levels, but did not restore the sAA and sulfhydryl abnormalities to normal levels. The increase that was observed in GSH after vitamin supplementation may have a beneficial effect in improving blood antioxidant status in uremic patients. Finally, the findings of elevated plasma Cys levels correlating to the elevated plasma Hcy levels in the presence of elevated plasma CSA levels, both before and after vitamin supplementation, led to the hypothesis that a block in decarboxylation of CSA is linked to hyperhomocysteinemia in end-stage renal failure.

BMJ. 1999 May 22;318(7195):1375-81.

Comment in: • ACP J Club. 1999 Nov-Dec;131(3):60. Efficacy of vitamin B-6 in the treatment of premenstrual syndrome: systematic review.

Wyatt KM, Dimmock PW, Jones PW, Shaughn O'Brien PM.

Academic Department of Obstetrics and Gynaecology, North Staffordshire Hospital, Stoke on Trent ST4 6QG.

OBJECTIVE: To evaluate the efficacy of vitamin B-6 in the treatment of premenstrual syndrome. DESIGN: Systematic review of published and unpublished randomised placebo controlled trials of the effectiveness of vitamin B-6 in the management of premenstrual syndrome. SUBJECTS: Nine published trials representing 940 patients with premenstrual syndrome. MAIN OUTCOME MEASURES: Proportion of women whose overall premenstrual symptoms showed an improvement over placebo. A secondary analysis was performed on the proportion of women whose premenstrual depressive symptoms showed an improvement over placebo. RESULTS: Odds ratio relative to placebo for an improvement in overall premenstrual symptoms was 2.32 (95% confidence interval 1.95 to 2.54). Odds ratio relative to placebo for an improvement in depressive symptoms was 1.69 (1.39 to 2.06) from four trials representing 541 patients. CONCLUSION: Conclusions are limited by the low quality of most of the trials included. Results suggest that doses of vitamin B-6 up to 100 mg/day are likely to be of benefit in treating premenstrual symptoms and premenstrual depression.

Can J Cardiol. 1999 Apr;15 Suppl B:31B-34B.

Homocyst(e)ine, vitamins and genetic interactions in vascular disease.

Malinow MR.

Oregon Health Sciences University, Portland, Oregon, USA. malinowr@ohsu.edu

Blood homocyst(e)ine levels are an important, independent and frequent risk factor for clinical atherosclerosis and venous thrombosis. Folic acid, vitamins B6 and B12, renal and thyroid functions, certain medications and certain genotypes are known to modulate plasma homocyst(e)ine levels. Intake of B vitamins through diet, supplementation and fortified foods effectively reduces homocyst(e)ine concentration and thus may reduce the risk of cardiovascular disease. This is true even in individuals who are genetically predisposed to hyperhomocyst(e)inemia. Randomized clinical trials are needed to investigate these effects further.

J Am Soc Nephrol. 1999 Apr;10(4):840-5. Intake of vitamins B6 and C and the risk of kidney stones in women.

Curhan GC, Willett WC, Speizer FE, Stampfer MJ.

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. gary.curhan@channing.harvard.edu

Urinary oxalate is an important determinant of calcium oxalate kidney stone formation. High doses of vitamin B6 may decrease oxalate production, whereas vitamin C can be metabolized to oxalate. This study was conducted to examine the association between the intakes of vitamins B6 and C and risk of kidney stone formation in women. The relation between the intake of vitamins B6 and C and the risk of symptomatic kidney stones were prospectively studied in a cohort of 85,557 women with no history of kidney stones. Semiquantitative food-frequency questionnaires were used to assess vitamin consumption from both foods and supplements. A total of 1078 incident cases of kidney stones was documented during the 14-yr follow-up period. A high intake of vitamin B6 was inversely associated with risk of stone formation. After adjusting for other dietary factors, the relative risk of incident stone formation for women in the highest category of B6 intake (> or =40 mg/d) compared with the lowest category (<3 mg/d) was 0.66 (95% confidence interval, 0.44 to 0.98). In contrast, vitamin C intake was not associated with risk. The multivariate relative risk for women in the highest category of vitamin C intake (> or =1500 mg/d) compared with the lowest category (<250 mg/d) was 1.06 (95% confidence interval, 0.69 to 1.64). Large doses of vitamin B6 may reduce the risk of kidney stone formation in women. Routine restriction of vitamin C to prevent stone formation appears unwarranted.

Nutr Metab Cardiovasc Dis. 1999 Apr;9(2):55-63.

Dietary vitamin B6 supplementation prevents ethanol-induced hypertension in rats.

Vasdev S, Wadhawan S, Ford CA, Parai S, Longerich L, Gadag V.

Department of Medicine, Memorial University of Newfoundland, St. John's, Canada.

BACKGROUND AND AIMS: All known pathways of ethanol metabolism result in the production of acetaldehyde, a highly reactive compound. Acetaldehyde has been shown to deplete vitamin B6 in chronic alcoholics. It also binds with sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels and increasing vascular cytosolic free calcium, peripheral vascular resistance and blood pressure. The aldehyde-binding thiol compound, N-acetyl cysteine, attenuates elevated blood pressure and associated adverse changes in ethanol-induced hypertensive rats. Vitamin B6 supplementation increases the level of endogenous cysteine. Aim of this work was thus to investigate whether a dietary supplementation of vitamin B6 can prevent ethanol-induced hypertension and associated changes in Wistar-Kyoto (WKY) rats. METHODS AND RESULTS: Starting at 7 weeks of age, WKY rats were divided into three groups of six animals each. The control group received a normal vitamin B6 diet (regular chow) and normal drinking water, the ethanol group, the same diet plus 1% ethanol in the drinking water, and the ethanol + vitamin B6 group a high vitamin B6 diet (20 times normal diet) and 1% ethanol in the drinking water. After 14 weeks, systolic blood pressure, platelet [Ca2+]i and kidney and aortic aldehyde conjugate levels were significantly higher in the ethanol group. These rats also showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. Dietary vitamin B6 supplementation prevented these changes. CONCLUSIONS: Dietary vitamin B6 supplementation prevented ethanol-induced hypertension and associated changes in WKY rats by normalizing tissue aldehyde conjugate levels.

Am J Cardiol. 1999 Mar 15;83(6):821-5. Reduction of homocysteine levels in coronary artery disease by low-dose folic acid combined with vitamins B6 and B12.

Lobo A, Naso A, Arheart K, Kruger WD, Abou-Ghazala T, Alsous F, Nahlawi M, Gupta A, Moustapha A, van Lente F, Jacobsen DW, Robinson K.

Department of Cardiology, The Cleveland Clinic Foundation, Ohio 44195, USA.

An increased plasma homocysteine concentration is a risk factor for atherosclerosis. Folic acid lowers homocysteine but the optimal dose in patients with coronary artery disease (CAD) is unclear. This placebo-controlled, single-blind, dose-ranging study evaluates the effect of low-dose folic acid on homocysteine levels in 95 patients aged 61 +/- 11 years (mean +/- SD) with documented CAD. Patients in each group were given either placebo or 1 of 3 daily supplements of folic acid (400 microg, 1 mg, or 5 mg) for 3 months. Each active treatment arm also received 500 microg vitamin B12 and 12.5 mg vitamin B6. Total plasma homocysteine levels were measured after 30 and 90 days. Folic acid 400 microg reduced homocysteine levels from 13.8 +/- 8.8 to 9.6 +/- 2.0 micromol/L at 90 days (p = 0.001). On 1- and 5-mg folic acid, levels decreased from 13.0 +/- 6.4 to 9.8 +/- 4.0 micromol/L (p = 0.001) and from 14.8 +/- 6.9 to 9.7 +/- 3.3 micromol/L (p < 0.001), respectively. The decrease was similar in all treatment groups. There was no significant change with placebo. Although the sample size is small, these findings suggest that daily administration of 400 microg/day folic acid combined with vitamin B12 and vitamin B6 may be equivalent to higher doses in reducing homocysteine levels in patients with CAD.

Treat News. 1999 Mar 5;(No 314):7-8.

Neuropathy: nutritional prevention/treatment suggested.

James JS.

AIDS: A simple regimen of calcium, magnesium, and vitamin B6 appears to prevent and treat peripheral neuropathy, a side effect of some drugs used to combat AIDS. Although the treatment has not been proven effective, anecdotal reports indicate that it works, and has few risks. Doctors can also use certain prescription drugs to alleviate the discomfort associated with neuropathy. In cases of severe neuropathy, doses of drugs may be reduced or stopped to prevent lasting nerve damage. Patients contemplating this regimen should know that significant overdoses of vitamin B6 can actually cause neuropathy.

Atherosclerosis. 1999 Mar;143(1):177-83. Combination of low-dose folic acid and pyridoxine for treatment of hyperhomocysteinaemia in patients with premature arterial disease and their relatives.

van der Griend R, Haas FJ, Biesma DH, Duran M, Meuwissen OJ, Banga JD.

Department of Internal Medicine, Sint Antonius Hospital, Nieuwegein, The Netherlands. r.griend@digd.azu.nl

Hyperhomocysteinaemia is an independent risk factor for atherosclerotic disease and venous thrombosis. The optimal homocysteine-lowering vitamin dose and target total homocysteine (tHcy) concentration are currently unknown. We prospectively studied the homocysteine-lowering effect after 8 weeks low-dose combination of folic acid (0.5 mg) and pyridoxine (100 mg) in 49 hyperhomocysteinaemic persons (33 patients with documented premature arterial disease and 16 of their first-degree relatives). Hyperhomocysteinaemia was in both sexes defined as fasting tHcy concentration > 12 micromol/l and/or post-methionine load tHcy concentration > 38 micromol/l. Low-dose vitamin therapy significantly reduced fasting tHcy concentration (median 13.9 to 9.3 micromol/l, reduction 32% (95% CI: 27-37%)) and post-load tHcy concentration (median 55.2 to 36.5 micromol/l, reduction 30% (95% CI: 25-35%)). Fasting tHcy reduction was similar in women and men, as well as in patients and relatives. Post-load tHcy reduction was significantly less in men compared to women (P = 0.04) and in relatives compared to patients (P = 0.03). Although low-dose combination of folic acid and pyridoxine results in a substantial reduction of tHcy concentrations (30-32%) in subjects with hyperhomocysteinaemia, the normalisation percentage to predefined criteria was less impressive (49%).

Br J Nutr. 1999 Mar;81(3):191-201.

Comment in: • Br J Nutr. 1999 Mar;81(3):175-6. Plasma pyridoxal phosphate and pyridoxic acid and their relationship to plasma homocysteine in a representative sample of British men and women aged 65 years and over.

Bates CJ, Pentieva KD, Prentice A, Mansoor MA, Finch S.

MRC Human Nutrition Research, Cambridge, UK. Chris.Bates@mrc-hnr.cam.ac.uk

Concentrations of pyridoxal phosphate and pyridoxic acid were measured in fasting plasma samples from British men and women aged 65 years and over, participating in a National Diet and Nutrition Survey during 1994-5, selected to be representative of the population of mainland Britain. In this population, the concentration of pyridoxal phosphate declined, whereas pyridoxic acid rose, with increasing age and frailty; however, both status indicators were strongly and directly (with a positive coefficient) correlated with estimates of vitamin B6 intake. This was little affected by the inclusion of food energy and protein intakes in the model. Forty-eight percent of the participants living in the community and 75% of those living in institutions had plasma pyridoxal phosphate concentrations below a range considered normal from other studies. In a univariate regression model, plasma pyridoxal phosphate concentrations were inversely correlated with plasma homocysteine concentrations, consistent with the hypothesis that vitamin B6 status may influence plasma homocysteine levels, and hence vascular disease risk. However, this relationship was partly attenuated in a multiple regression model including age, sex, domicile and biochemical status indices, including those of folate and vitamin B12. There was evidence that plasma pyridoxal phosphate was sensitive to metabolic conditions associated with inflammation and the acute-phase reaction, and that plasma pyridoxic acid was sensitive to renal function. Thus, neither index is an ideal predictor of vitamin B6 status in older people, unless these confounding factors are allowed for. Since poor vitamin B6 status may have health implications, e.g. for immune function, cognition, and for essential intermediary metabolic pathways in older people, it needs to be investigated as a possible public health problem.

60: Marks J. Vitamin B-6. Many have found relief from disorders for which no effective treatment exists. BMJ. 1999 Feb 13;318(7181):463. No abstract available. PMID: 9974473

Zh Nevrol Psikhiatr Im S S Korsakova. 1999;99(1):37-41.

[Cerebrolysin and magnesium-B6 in the treatment of side effects of psychotropic drugs]

[Article in Russian]

Panteleeva GP, Bondar' VV, Krasnikova NI, Raiushkin VA.

51 patients were observed. Schizophrenia was diagnosed in 31 patients and endogenous depression in 20 cases. All the patients had extrapyramidal and somato-vegetative side effects of neuroleptics and antidepressive drugs, and were resistant to conventional corrective therapy for at least a period of 3 weeks. In addition to current treatment of both basic disease and adverse effects, cerebrolysin was administered (5-10 ml i.v./dr, during 28 days) and magme B6 (20-30 ml per os during 21 days). By the treatment end-point either moderate or marked reduction of extrapyramidal disorders (according to ESRS) was observed in 74.4% of patients treated by cerebrolysin and in 72.2% treated by magne B6; somato-vegetative adverse effects reduced (by SARS) in 85.8% and in 83.8% respectively. Both drugs showed equally high efficacy against hyperkinetic and cardiovascular side effects (symptoms relief was in 59-62% and 65-69%, respectively). Cerebrolysin is more preferable in cases of side vegetative events, dysomnia and dysuria; magne B6 was more effective in correction of akineto-hypertonic and hyperkinetic-hypertonic syndromes as well as in cholinolytic side effects.

Alcohol Alcohol. 1998 Nov-Dec;33(6):631-8. Benfotiamine in treatment of alcoholic polyneuropathy: an 8-week randomized controlled study (BAP I Study).

Woelk H, Lehrl S, Bitsch R, Kopcke W.

Psychiatrisches Krankenhaus, Giessen, Germany.

A three-armed, randomized, multicentre, placebo-controlled double-blind study was used to examine the efficacy of benfotiamine vs a combination containing benfotiamine and vitamins B6 and B12 in out-patients with severe symptoms of alcoholic polyneuropathy (Benfotiamine in treatment of Alcoholic Polyneuropathy, BAP I). The study period was 8 weeks and 84 patients fulfilled all the prerequisite criteria and completed the study as planned. Benfotiamine led to significant improvement of alcoholic polyneuropathy. Vibration perception (measured at the tip of the great toe) significantly improved in the course of the study, as did motor function. and the overall score reflecting the entire range of symptoms of alcoholic polyneuropathy. A tendency toward improvement was evident for pain and co-ordination; no therapy-specific adverse effects were seen.

Biochim Biophys Acta. 1998 Aug 24;1381(3):351-4.

Effect of pyridoxine and insulin administration on brain glutamate dehydrogenase activity and blood glucose control in streptozotocin-induced diabetic rats.

Nair AR, Biju MP, Paulose CS.

Molecular Neurobiology and Cell Biology Unit, Department of Biotechnology, Cochin University of Science and Technology, Cochin 682 022, India.

Blood glucose level and kinetic parameters of glutamate dehydrogenase (GDH) were measured in the cerebellum, brain stem and cerebral cortex of control, insulin treated, pyridoxine treated, pyridoxine and insulin treated and untreated streptozotocin-diabetic rats. The combined administration of insulin and pyridoxine was found to be better in controlling the hyperglycaemia. Insulin with pyridoxine treatment brought back the increased maximal velocity of GDH during diabetes to control state. Also, there was an increase in Michaelis-Menten constant. These results suggest that pyridoxine and insulin together serve a better control for diabetes. Copyright Elsevier Science B.V.

Am J Clin Nutr. 1998 Aug;68(2):389-95. Riboflavin and vitamin B-6 intakes and status and biochemical response to riboflavin supplementation in free-living elderly people.

Madigan SM, Tracey F, McNulty H, Eaton-Evans J, Coulter J, McCartney H, Strain JJ.

Human Nutrition Research Group, University of Ulster, Coleraine, Northern Ireland.

Free-living elderly people aged > or = 65 y were recruited to assess riboflavin and vitamin B-6 intakes and status and the effect of riboflavin supplementation on biochemical indicators of these 2 vitamins. The status of riboflavin (erythrocyte glutathione reductase activation coefficient; EGRAC) and vitamin B-6 (plasma pyridoxal-5'-phosphate; PLP) were determined in a total sample of 92 subjects, from whom dietary intake data were obtained by using the diet history method (n = 83). Although dietary intakes of both vitamins were considered to be adequate according to current reference values, abnormal EGRAC and plasma PLP values were identified in 49% and 38% of subjects, respectively, with 21% having suboptimal status for both nutrients. A subgroup of subjects from the initial sample (n = 45) was assigned in a double-blind manner to receive either 1.6 or 25 mg riboflavin or placebo daily for 12 wk. In those subjects with a baseline EGRAC or plasma PLP value falling outside the currently accepted threshold value for adequacy, low-dose riboflavin supplementation improved status of the limiting nutrient significantly (P<0.0001 and P = 0.020 for EGRAC and plasma PLP responses, respectively). We conclude that a high proportion of healthy elderly people may have suboptimal status for these nutrients despite apparently adequate dietary intakes. Furthermore, we showed that riboflavin supplementation at physiologic doses corrects biochemical abnormalities of not only EGRAC, but also plasma PLP, confirming the biochemical interdependency of these vitamins and suggesting that riboflavin is the limiting nutrient.

Am J Obstet Gynecol. 1998 Jul;179(1):135-9. Effects of folic acid and vitamin B6 supplementation on women with hyperhomocysteinemia and a history of preeclampsia or fetal growth restriction.

Leeda M, Riyazi N, de Vries JI, Jakobs C, van Geijn HP, Dekker GA.

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Free University Hospital, Amsterdam, The Netherlands.

OBJECTIVE: Our purpose was to assess the incidence of hyperhomocysteinemia in patients with a history of preeclampsia or fetal growth restriction, to evaluate the effects of vitamin supplementation on the methionine loading test, and to study the course of subsequent pregnancies in women with hyperhomocysteinemia and a history of preeclampsia or fetal growth restriction. STUDY DESIGN: A total of 207 consecutive patients with a history of preeclampsia or fetal growth restriction was tested for hyperhomocysteinemia. Thirty-seven were found to be positive and were treated with folic acid and vitamin B6, and 27 had a second methionine loading test after vitamin supplementation. Fourteen patients became pregnant again while receiving vitamins and aspirin. RESULTS: All patients who underwent a methionine loading test after vitamin supplementation had a completely normalized methionine loading test. Of the 14 pregnancies in women receiving vitamins and aspirin, 7 were complicated by preeclampsia. Birth weights were 2867 +/- 648 g compared with 1088 +/- 570 g in the previous pregnancies. CONCLUSIONS: Vitamin B6 and folic acid correct the methionine loading test in patients with hyperhomocysteinemia. Perinatal outcome in patients with a history of preeclampsia or fetal growth restriction and hyperhomocysteinemia appears to be favorable.

Natl Med J India. 1998 Jul-Aug;11(4):171-2.

Effect of pyridoxine or riboflavin supplementation on plasma homocysteine levels in women with oral lesions.

Lakshmi AV, Ramalakshmi BA.

National Institute of Nutrition, Indian Council of Medical Research, Andhra Pradesh, India.

BACKGROUND: A moderate increase in plasma homocysteine level has been reported to be involved in neural tube defects, which can be prevented with folic acid supplementation. Folic acid, vitamins B6- and B12-dependent enzymes are required to metabolize homocysteine. A study in rats showed higher tissue homocysteine levels in riboflavin as well as pyridoxine deficiency. We studied the effect of treatment with pyridoxine or riboflavin on plasma total homocysteine concentration in women with clinical and biochemical deficiencies of riboflavin and pyridoxine. METHODS: Plasma total homocysteine concentrations were measured in 20 women with glossitis and angular stomatitis before and after supplementation with pyridoxine or riboflavin. RESULTS: Pyridoxine treatment significantly reduced plasma homocysteine concentration while riboflavin treatment did not have a significant effect. CONCLUSIONS: Plasma total homocysteine levels tended to be higher in women with clinical and biochemical deficiency of vitamin B6 and therapy with pyridoxine reduced its level significantly. Riboflavin supplementation did not have a significant impact on plasma homocysteine concentration in women with glossitis and angular stomatitis.

Res Exp Med (Berl). 1998 Jul;198(1):37-42. Vitamin supplementation during weight reduction--favourable effect on homocysteine metabolism.

Henning BF, Tepel M, Riezler R, Gillessen A, Doberauer C.

Med. Klinik I, Univ.-Klinik Marienhospital, Herne, Germany.

Moderately elevated homocysteine concentrations, reflecting deficiency of some nutritional factors required for homocysteine metabolism (folate, vitamin B-6, vitamin B-12) and/or less severe genetic defects, are common in the general population. Several studies have indicated the role of homocysteine as an independent risk factor for vascular disease. A pilot study published recently suggested that plasma homocysteine levels increase during weight reduction in slightly overweight, otherwise healthy subjects (group A). We examined a comparable group of 13 overweight subjects (group B) using a standardised caloric intake and defined vitamin supplementation (Medyn: folate 0.2 mg/ vitamin B-68.0 mg/ vitamin B-120.010 mg three times the day orally) to determine the effect of weight reduction on serum homocysteine levels and to compare the results with those of the pilot study. Mean body weight declined from 87.0 +/- 20.2 to 84.2 +/- 20.1 kg (P < 0.05) in group A and 85.7 +/- 11.3 to 82.5 +/- 9.9 kg (P = 0.049) in group B. Serum homocysteine levels rose from 7.9 +/- 2.0 to 8.7 +/- 2.3 mumol/l (P < 0.0001) in group A and decreased from 8.19 +/- 1.73 to 7.35 +/- 0.88 mumol/l (P = 0.0022) in group B. No correlation was found between the changes in body weight and in homocysteine levels (r = 0.02 in group A, r = 0.18 in group B). Additionally, no correlation was found between serum folate levels and changes in homocysteine levels (r = 0.03 in group A, r = 0.09 in group B). The results suggest that an adequate oral vitamin-supplementation protects against increased homocysteine production during weight reduction.

Clin Cancer Res. 1998 Jun;4(6):1567-71.

Efficacy of pyridoxine to ameliorate the cutaneous toxicity associated with doxorubicin containing pegylated (Stealth) liposomes: a randomized, double-blind clinical trial using a canine model.

Vail DM, Chun R, Thamm DH, Garrett LD, Cooley AJ, Obradovich JE.

Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison 53706, USA. vaild@svm.vetmed.wisc.edu

A cutaneous reaction termed palmar-plantar erythrodysesthesia (PPES) or hand-foot syndrome can be dose limiting for Doxil, a doxorubicin containing pegylated (Stealth) liposome. The objective of this study was to determine the ability of concomitant pyridoxine therapy to prevent the development of PPES during Doxil therapy. Forty-one dogs with non-Hodgkin's lymphoma were randomized in a double-blind fashion to receive either oral pyridoxine or placebo daily during Doxil chemotherapy (1.0 mg/kg, i.v., every 3 weeks for a total of five treatments). Cutaneous toxicity was determined by clinical and histological scoring. No difference was observed in remission rates (71.4 versus 75%) achieved between groups. The likelihood of developing serious PPES and having to decrease or discontinue Doxil therapy was 4.2 times (relative risk) greater in placebo group dogs than in pyridoxine group dogs (P = 0.032). Pyridoxine did not completely abrogate PPES; however, it occurred later and less dramatically than in placebo-treated dogs and resulted in fewer treatment delays or discontinuations, allowing a higher cumulative dose of Doxil to be received. Compared to the 5.0 mg/kg cumulative target dose, pyridoxine-treated dogs received a median cumulative dose of 4.7 mg/kg (mean, 4.1 mg/kg), and the placebo-treated dogs received a median of 2.75 mg/kg (mean, 2.9 mg/kg; P < 0.028). A trend (P = 0.084) toward prolongation of remission length was observed in dogs receiving pyridoxine, which was likely attributable to their ability to receive more Doxil without delay or discontinuation. We conclude that pyridoxine is effective in delaying the onset and severity of PPES in this canine model.

Am J Clin Nutr. 1998 May;67(5):858-66.

Erratum in: • Am J Clin Nutr 1998 Sep;68(3):758.

Comment in: • Am J Clin Nutr. 1999 Jun;69(6):1287-9. Effect of B-group vitamins and antioxidant vitamins on hyperhomocysteinemia: a double-blind, randomized, factorial-design, controlled trial.

Woodside JV, Yarnell JW, McMaster D, Young IS, Harmon DL, McCrum EE, Patterson CC, Gey KF, Whitehead AS, Evans A.

School of Clinical Medicine, The Queen's University of Belfast, United Kingdom. p9495754@qub.ac.uk

Mild hyperhomocysteinemia is accepted as a risk factor for premature cardiovascular disease. In a population with a high prevalence of cardiovascular disease, we screened a group of clinically healthy working men aged 30-49 y (n = 509) for plasma homocysteine and 5,10-methylene tetrahydrofolate reductase (MTHFR) genotype status. Those with mildly elevated homocysteine concentrations (> or = 8.34 micromol/L) were selected for intervention. In a randomized, factorial-design, controlled trial we assessed the effects of B-group vitamins and antioxidant vitamin supplementation on homocysteine concentrations. The 132 men were randomly assigned to one of four groups: supplementation with B-group vitamins alone (1 mg folic acid, 7.2 mg pyridoxine, and 0.02 mg cyanocobalamin), antioxidant vitamins alone (150 mg ascorbic acid, 67 mg RRR-alpha-tocopherol, and 9 mg beta-carotene), B-group vitamins with antioxidant vitamins, or placebo. Intervention was double-blind. A total of 101 men completed the 8-wk intervention. When homocysteine concentrations were analyzed by group, significant (P < 0.001) decreases (32.0% and 30.0%, respectively) were observed in both groups receiving B-group vitamins either with or without antioxidants. The effect of B-group vitamins alone over 8 wk was a reduction in homocysteine concentrations of 27.9% (95% CI: 22.0%, 33.3%; P < 0.001) whereas antioxidants alone produced a nonsignificant increase of 5.1% (95% CI: -2.8%, 13.6%; P = 0.21). There was no evidence of any interaction between the two groups of vitamins. The effect of B-group vitamin supplementation seemed to depend on MTHFR genotype. Supplementation with the B-group vitamins with or without antioxidants reduced homocysteine in the men with mildly elevated concentrations, and hence may be effective in reducing cardiovascular risk.

Neuromuscul Disord. 1998 May;8(3-4):210-2.

Effect of vitamin B6 supplementation in McArdle's disease: a strategic case study.

Phoenix J, Hopkins P, Bartram C, Beynon RJ, Quinlivan RC, Edwards RH.

Department of Biomolecular Science, UMIST, Manchester, UK.

A patient-blind study into the effect of a 10-week cessation of long-term vitamin B6 supplementation on B6 status and performance in McArdle's disease is reported. Muscle performance was assessed both subjectively and objectively by an ischaemic fatiguing protocol of the adductor pollicis muscle. Nine weeks after withdrawal of supplementation, vitamin B6 status had changed from adequacy to inadequacy and the force loss during the ischaemic fatiguing protocol had increased at all frequencies studied. The patient reported decreased exercise tolerance after 7 weeks and by the tenth week was experiencing an increase in muscle cramps. Vitamin B6 status and muscle performance may be linked in McArdle's disease and there is potential for enhancement of performance by B6 supplementation.

71: [No authors listed] Can J Cardiol. 1999 Apr;15 Suppl B:31B-34B.

Homocyst(e)ine, vitamins and genetic interactions in vascular disease.

Malinow MR.

Oregon Health Sciences University, Portland, Oregon, USA. malinowr@ohsu.edu

Blood homocyst(e)ine levels are an important, independent and frequent risk factor for clinical atherosclerosis and venous thrombosis. Folic acid, vitamins B6 and B12, renal and thyroid functions, certain medications and certain genotypes are known to modulate plasma homocyst(e)ine levels. Intake of B vitamins through diet, supplementation and fortified foods effectively reduces homocyst(e)ine concentration and thus may reduce the risk of cardiovascular disease. This is true even in individuals who are genetically predisposed to hyperhomocyst(e)inemia. Randomized clinical trials are needed to investigate these effects further. . Harv Health Lett. 1998 Apr;23(6):8. No abstract available. PMID: 9577258

72: den Heijer M, Brouwer IA, Bos GM, Blom HJ, van der Put NM, Spaans AP, Rosendaal FR, Thomas CM, Haak HL, Wijermans PW, Gerrits WB. Vitamin supplementation reduces blood homocysteine levels: a controlled trial in patients with venous thrombosis and healthy volunteers. Arterioscler Thromb Vasc Biol. 1998 Mar;18(3):356-61. PMID: 9514403

J Indian Med Assoc. 1998 Mar;96(3):82-3.

Assessment of efficacy of pyridoxine in control of radiation induced sickness.

Mahajan MK, Singh V.

Department of Radiotherapy, Christian Medical College, Ludhiana.

A randomised prospective study to evaluate the role of adjuvant administration of pyridoxine hydrochloride was carried out in 104 patients undergoing radiation therapy. In study group 52 patients received tablet pyridoxine (controlled release) 100 mg daily one hour before the radiation therapy, for a period of 7 days, while the control group was treated by irradiation alone. Reduced radiation induced sickness was observed in study group (32.6% versus 48.1%). Loss of appetite (0% versus 1.9%), nausea (11.5% versus 21.1%) and vomiting (21.1% versus 28.8%) were lower for pyridoxine treated patients than for control patients. The above observed reduction in radiation induced sickness was found to be statistically insignificant (p > 0.05). The present data also did not reveal a statistical correlation between integral dose and radiation sickness.

J Nephrol. 1998 Mar-Apr;11 Suppl 1:49-50. Pyridoxine-responsive PH1: treatment.

Toussaint C.

Departement medico-chirurgical de Nephrologie, Cliniques Universitaires de Bruxelles, Hopital Erasme, Belgium.

Owing to the rarity of PH, the efficacy of pyridoxine therapy has only been tested in very small series of patients. From two recent reports including 18 patients, 50% of patients would be unresponsive to pyridoxine whereas oxaluria would be normalized in 20% of patients and somewhat reduced-but not to normal level-in the remaining 30%. In a few aneodotical cases pyridoxine administration was reported to improve kidney function in patients with renal failure secondary to hyperoxaluria. It is reminded that megadoses of pyridoxine (0.5 to 6 g daily) may induce severe sensory neuropathy.

JAMA. 1998 Feb 4;279(5):359-64.

Comment in: • JAMA. 1998 Aug 5;280(5):417-8; author reply 418-9. • JAMA. 1998 Aug 5;280(5):417; author reply 418-9. • JAMA. 1998 Aug 5;280(5):418-9. • JAMA. 1998 Aug 5;280(5):418; author reply 418-9. • JAMA. 1998 Aug 5;280(5):418; author reply 418-9. • JAMA. 1998 Feb 4;279(5):392-3. Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women.

Rimm EB, Willett WC, Hu FB, Sampson L, Colditz GA, Manson JE, Hennekens C, Stampfer MJ.

Department of Epidemiology, Harvard School of Public Health, Boston, Mass 02115, USA. eric.rimm@channing.harvard.edu

CONTEXT: Hyperhomocysteinemia is caused by genetic and lifestyle influences, including low intakes of folate and vitamin B6. However, prospective data relating intake of these vitamins to risk of coronary heart disease (CHD) are not available. OBJECTIVE: To examine intakes of folate and vitamin B6 in relation to the incidence of nonfatal myocardial infarction (MI) and fatal CHD. DESIGN: Prospective cohort study. SETTING AND PATIENTS: In 1980, a total of 80082 women from the Nurses' Health Study with no previous history of cardiovascular disease, cancer, hypercholesterolemia, or diabetes completed a detailed food frequency questionnaire from which we derived usual intake of folate and vitamin B6. MAIN OUTCOME MEASURE: Nonfatal MI and fatal CHD confirmed by World Health Organization criteria. RESULTS: During 14 years of follow-up, we documented 658 incident cases of nonfatal MI and 281 cases of fatal CHD. After controlling for cardiovascular risk factors, including smoking and hypertension and intake of alcohol, fiber, vitamin E, and saturated, polyunsaturated, and trans fat, the relative risks (RRs) of CHD between extreme quintiles were 0.69 (95% confidence interval [CI], 0.55-0.87) for folate (median intake, 696 microg/d vs 158 microg/d) and 0.67 (95% CI, 0.53-0.85) for vitamin B6 (median intake, 4.6 mg/d vs 1.1 mg/d). Controlling for the same variables, the RR was 0.55 (95% CI, 0.41-0.74) among women in the highest quintile of both folate and vitamin B6 intake compared with the opposite extreme. Risk of CHD was reduced among women who regularly used multiple vitamins (RR=0.76; 95% CI, 0.65-0.90), the major source of folate and vitamin B6, and after excluding multiple vitamin users, among those with higher dietary intakes of folate and vitamin B6. In a subgroup analysis, compared with nondrinkers, the inverse association between a high-folate diet and CHD was strongest among women who consumed up to 1 alcoholic beverage per day (RR =0.69; 95% CI, 0.49-0.97) or more than 1 drink per day (RR=0.27; 95% CI, 0.13-0.58). CONCLUSION: These results suggest that intake of folate and vitamin B6 above the current recommended dietary allowance may be important in the primary prevention of CHD among women.

Am J Clin Nutr. 1998 Feb;67(2):208-20. Vitamin B-6 requirement and status assessment of young women fed a high-protein diet with various levels of vitamin B-6.

Huang YC, Chen W, Evans MA, Mitchell ME, Shultz TD.

Department of Food Science and Human Nutrition, Washington State University, Pullman 99164-6376, USA.

The vitamin B-6 requirement of young women consuming a constant high-protein diet (1.55 g/kg body wt) and the effect of various ratios of vitamin B-6 to protein on this requirement were studied. Eight women were fed a lactoovovegetarian basal diet containing 0.45 mg vitamin B-6 (2.66 micromol as pyridoxine) and 30 micromol carnitine for 92 d. The protocol consisted of successive baseline adjustment (9 d), depletion (27 d), and repletion (two 21-d and then one 14-d) periods. Vitamin B-6 intakes were 1.60, 0.45, 1.26, 1.66, and 2.06 mg, resulting in ratios of vitamin B-6 (in mg) to protein (in g) for the five periods of 0.016, 0.005, 0.013, 0.017, and 0.021, respectively. Direct and indirect as well as short- and long-term vitamin B-6 status measures were assessed weekly. Regression analysis revealed that the amount of dietary vitamin B-6 required to normalize urinary 4-pyridoxic acid, plasma pyridoxal-P, erythrocyte pyridoxal-P and pyridoxal, and erythrocyte alanine and aspartate aminotransferase activity coefficients to predepletion baseline values was 1.94 mg vitamin B-6/d (0.019 mg vitamin B-6/g protein). This study suggests that the current vitamin B-6 recommended dietary allowance of 1.6 mg/d based on 0.016 mg/g protein is not an adequate intake and may require reevaluation.

Int J Vitam Nutr Res. 1998;68(2):98-103.

Folic acid and Vitamin B6 supplementation and plasma homocysteine concentrations in healthy young women.

Dierkes J, Kroesen M, Pietrzik K.

Dept. of Pathophysiology of Human Nutrition, University of Bonn., Germany.

Elevated plasma homocysteine levels are a risk factor for atherosclerotic disease. Elevated fasting plasma homocysteine concentrations can be reduced by vitamin supplementation with folic acid, vitamin B6 and vitamin B12, but the effect of nutritive amounts of single vitamins on homocysteine plasma levels within the normal range is not known. This study was performed to investigate the effect of folic acid supplementation (400 micrograms/d) on fasting plasma homocysteine levels in healthy young women, in comparison to vitamin B6 (2 mg/d) or a combination of both vitamins. Healthy young women with normal homocysteine levels were supplemented for four weeks either with folic acid, vitamin B6 or the combination. The combination of folic acid and vitamin B6 reduced plasma homocysteine by 17%. Supplementation with folic acid reduced plasma homocysteine levels by 11.5%. The effect of folic acid and vitamin B6 was not significantly different from the effect of folic acid alone. Vitamin B6 had no effect on plasma homocysteine concentrations. Results show that homocysteine levels within the normal range are lowered by low-dose vitamin supplementation including folic acid.

J Hepatol. 1998 Jan;28(1):54-60.

Comment in: • J Hepatol. 1999 Apr;30(4):739-40.

Metadoxine accelerates fatty liver recovery in alcoholic patients: results of a randomized double-blind, placebo-control trial. Spanish Group for the Study of Alcoholic Fatty Liver.

Caballeria J, Pares A, Bru C, Mercader J, Garcia Plaza A, Caballeria L, Clemente G, Rodrigo L, Rodes J.

Liver Unit, Hospital Clinic i Provincial, University of Barcelona, Spain. rovira@medicina.ub.es

BACKGROUND/AIMS: Our aim was to investigate the effectiveness of metadoxine (pyridoxol L, 2 pyrrolidone-5-carboxylate) in the treatment of alcoholic fatty liver. METHODS: A double-blind randomized multicenter trial involving 136 chronic active alcoholic patients diagnosed with fatty liver by clinical, biochemical and ultrasonographic criteria was performed. Patients were treated with 1500 mg/day of metadoxine (n = 69) or placebo (n = 67) for 3 months. Patients were clinically and biochemically evaluated every month. Ultrasonography was performed before and after treatment. RESULTS: At the end of the study there was a significant improvement in the liver function tests in both groups. However, the changes were more rapid and greater in patients treated with metadoxine, in whom significant changes in serum levels of bilirubin, aminotransferases and gammaglutamyl transpeptidase were already observed after 1 month of treatment, and normalization of these parameters was observed at the end. After treatment, the percentage of patients with ultrasonographic signs of steatosis was significantly lower in the metadoxine group (28% vs 70%, p < 0.01) and the degree of steatosis was also lower in this group. Sixteen patients treated with metadoxine and 15 with placebo continued drinking. Alcohol intake was lower than initially, and similar in both groups. In the metadoxine group, the biochemical changes were similar in both the abstinent and the nonabstinent patients. In contrast, in the placebo group the improvement in the liver function tests was significantly higher in abstinents. Among patients who continued drinking, the prevalence (45% vs 92%, p < 0.05) and the degree of steatosis were also significantly lower in patients treated with metadoxine. CONCLUSIONS: In patients with alcoholic fatty liver, metadoxine accelerates the normalization of liver function tests and the ultrasonographic changes, even in those who do not completely abstain from alcohol intake. Thus, metadoxine could be useful in the treatment of the early stages of alcoholic liver disease.

J Psychopharmacol. 1998;12(2):220-1.

High-dose vitamin E plus vitamin B6 treatment of risperidone-related neuroleptic malignant syndrome.

Dursun SM, Oluboka OJ, Devarajan S, Kutcher SP.

Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada. sdursun@is.dal.ca

We present a case of a 74-year-old patient with schizoaffective disorder, who developed risperidone-related neuroleptic malignant syndrome. This patient responded satisfactorily to the supportive management and vit E plus vit B6.

Urol Int. 1998;60(2):105-7. Magnesium hydrogen carbonate natural mineral water enriched with K(+)-citrate and vitamin B6 improves urinary abnormalities in patients with calcium oxalate nephrolithiasis.

Bren A, Kmetec A, Kveder R, Kaplan-Pavlovcic S.

Department of Nephrology, University Medical Center, Ljubljana, Slovenia. Andrej.Bren@mf.uni-lj.si

The influence of drinking magnesium hydrogen carbonate natural mineral water enriched with potassium citrate on urinary metabolic abnormalities was prospectively studied in 27 patients with recurrent calcium oxalate nephrolithiasis. The mean 24-hour urinary pH shifted from 6.34 to 6.93 (p < 0.01), the mean urinary magnesium/urinary creatinine ratio rose from 0.47 to 0.67 (p < 0.01), the mean urinary citrate/urinary creatinine ratio increased from 0.26 to 0.35 (p NS), and the mean 24-hour urinary calcium decreased from 7.98 to 6.05 mmol (p < 0.05). The effects of magnesium hydrogen carbonate natural mineral water enriched with potassium citrate were found to be favorable on urinary calcium, urinary magnesium/urinary creatinine ratio and urinary pH in patients with calcium oxalate nephrolithiasis.

Zh Nevrol Psikhiatr Im S S Korsakova. 1998;98(9):30-2.

[Diabetic polyneuropathy treatment by milgamma-100 preparation]

[Article in Russian]

Sadekov RA, Danilov AB, Vein AM.

Efficiency of Milgamma-100 preparation (100 mg of benfothiamine + 100 mg of pyridoxin) was studied in treatment of diabetic polyneuropathy in 14 patients with diabetes mellitus type II (1 dragee 3 times a day, within 6 weeks). After the course of treatment the intensity of pains was decreased according to visual analogous scale on the average from 8.2 to 2.3 scores, the indices of vibratory sensitivity improved significantly as well as the data of cardiovascular tests characterizing parasympathetic control of heart rhythm. Meanwhile latent periods of the evoked sympathetic potentials on arms and legs which were initially lengthened became significantly shorter. A clear-cut tendency was also found to increasing conduction rate for excitation through the motor nerves. The treatment resulted in the improvement of the condition in 93% of the cases. The conclusion was made about efficiency and safety of Milgamma-100 preparation application in therapy of patients with diabetic polyneuropathy.

J Intern Med. 1997 Jul;242(1):79-81.

Pyridoxin-responsive anaemia in a patient with a history of polycythaemia vera.

Van Gameren II, Wijnja L, Louwes H, de Wolf JT.

Department of Internal Medicine, Martini Hospital, van Swietenlaan, The Netherlands.

Pancytopenia in the course of polycythaemia vera (PV) following the proliferative and stable phase, ultimately leads to a spent phase characterized by extensive marrow fibrosis. We describe a patient with a history of PV and pancytopenia caused by myelodysplasia, before a genuine end stage myelofibrosis had occurred. The related anaemia was responsive to pyridoxin.

Pediatr Neurol. 1997 Jul;17(1):54-7. Randomized, controlled trial of high-dose intravenous pyridoxine in the treatment of recurrent seizures in children.

Jiao FY, Gao DY, Takuma Y, Wu S, Liu ZY, Zhang XK, Lieu NS, Ge ZL, Chui W, Li HR, Cao YM, Bai AN, Liu SB.

Department of Pediatrics, Shaanxi Provincial People's Hospital, Xian, P.R. China.

To determine the efficacy of pyridoxine in treating seizures, 90 infants and children with recurrent convulsions primarily due to acute infectious diseases were enrolled in the present study. Forty patients were treated with high-dose pyridoxine (30 or 50 mg/kg/day) by intravenous infusion, and 50 subjects served as controls. Antiepileptic drugs and other therapies were similar in the two groups except for pyridoxine. Clinical efficacy criteria were based on the frequency of convulsions per day and on the duration of individual seizures after therapy was initiated. The results indicated that total response rates in the pyridoxine group and control group were 92.5% and 64%, respectively (chi-square = 14.68, P < .001). After initiation of therapy, seizures resolved after 2.4 +/- 1.4 days in the pyridoxine group and after 3.7 +/- 2.0 days in the control group (t = 3.67, P < .001). No adverse effects of pyridoxine were apparent during the observation period. We conclude that pyridoxine is an effective, safe, well-tolerated, and relatively inexpensive adjunct to routine antiepileptic drugs for treatment of recurrent seizures in children.

J Nutr. 1997 Jun;127(6):1219-28. Chronic exercise affects vitamin B-6 metabolism but not requirement of growing rats.

Hadj-Saad F, Lhuissier M, Guilland JC.

Laboratoire de Physiologie, Faculte de Medecine, Dijon, France.

The effect of chronic exercise (forced swimming) on vitamin B-6 status and metabolism was studied in growing male rats fed deficient (0 mg pyridoxine-HCl/kg), suboptimal (2 mg pyridoxine-HCl/kg) or control (7 mg pyridoxine-HCl/kg) diets for 9 wk. Sedentary rats were fed the same diets. Body weight gain was lower in deficient rats than in both other dietary groups. Sedentary rats were heavier than trained rats of all diet groups. Erythrocyte aspartate aminotransferase, urinary 4-pyridoxic acid excretion, blood (plasma and erythrocytes) and tissue B-6 vitamers were measured. Urinary 4-pyridoxic acid, plasma pyridoxal 5'-phosphate and erythrocyte aspartate aminotransferase values of exercised and sedentary rats responded to changes in dietary pyridoxine but were not different from one another. After 9 wk of vitamin B-6 depletion, tissue concentrations of pyridoxal 5'-phosphate and pyridoxamine 5;5'-phosphate were 41-66% and 26-49% lower, respectively, in the deficient groups than in the control groups. Larger percentage differences occurred in plasma than in tissues (95 vs. 22-66%). In liver, pyridoxal 5'-phosphate concentrations were lower, whereas pyridoxal concentrations were higher in trained than in sedentary rats. In gastrocnemius muscle, pyridoxal 5'-phosphate, pyridoxamine 5'-phosphate and total vitamin B-6 concentrations were higher in trained than in sedentary rats. Concentrations of vitamin B-6 compounds in heart, kidneys, brain and adrenals were not affected by training. On the basis of the vitamin B-6-dependent variables measured in this study, we conclude that prolonged exercise affects the metabolism of vitamin B-6, but does not increase the vitamin B-6 requirement in growing rats.

Ann Epidemiol. 1997 May;7(4):285-93. Vitamin intake: a possible determinant of plasma homocyst(e)ine among middle-aged adults.

Shimakawa T, Nieto FJ, Malinow MR, Chambless LE, Schreiner PJ, Szklo M.

Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Bethesda, MD, USA.

PURPOSE: Many epidemiologic studies have identified elevated plasma homocyst(e)ine as a risk factor for atherosclerosis and thromboembolic disease. To examined the relationship between vitamin intakes and plasma homocyst(e)ine, we analyzed dietary intake data from a case-control study of 322 middle-aged individuals with atherosclerosis in the carotid artery and 318 control subjects without evidence of this disease. METHODS: All of these individuals were selected from a probability sample of 15,800 men and women who participated in the Atherosclerosis Risk in Communities (ARIC) Study. RESULTS: Plasma homocyst(e)ine was inversely associated with intakes of folate, vitamin B6, and vitamin B12 (controls only for this vitamin)--the three key vitamins in homocyst(e)ine metabolism. Among nonusers of vitamin supplement products, on average each tertile increase in intake of these vitamins was associated with 0.4 to 0.7 mumol/L decrease in plasma homocyst(e)ine. An inverse association of plasma homocyst(e)ine was also found with thiamin, riboflavin, calcium, phosphorus, and iron. Methionine and protein intake did not show any significant association with plasma homocyst(e)ine. CONCLUSIONS: In almost all analyses, cases and controls showed similar associations between dietary variables and plasma homocyst(e)ine. Plasma homocyst(e)ine among users of vitamin supplement products was 1.5 mumol/L lower than that among nonusers. Further studies to examine possible causal relationships among vitamin intake, plasma homocyst(e)ine, and cardiovascular disease are needed.

86: Kurlemann G, Deufel T, Schuierer G. Pyridoxine--responsive West syndrome and gamma-aminobutyric acid. Eur J Pediatr. 1997 Feb;156(2):158-9. No abstract available. PMID: 9039527

87: Ray M, Kumar L, Prasad R. Homocystinuria with early thromboembolic episodes and rapid response to high dose pyridoxine. Indian Pediatr. 1997 Jan;34(1):67-9. No abstract available. PMID: 9251284

88: Salhany JM, Stevenson M. Hypothesis: potential utility of pyridoxal 5'-phosphate (vitamin B6) and levamisole in immune modulation and HIV-1 infection. AIDS Patient Care STDS. 1996 Dec;10(6):353-6. Review. No abstract available. PMID: 11361551

Fortschr Med. 1996 Nov 20;114(32):439-43.

[Medicamentous therapy of alcoholic polyneuropathy. Randomized double-blind study comparing 2 vitamin B preparations and a nucleotide preparation]

[Article in German]

Kretschmar C, Kaumeier S, Haase W.

III. Psychiatrische Klinik, Klinik fur Suchtkrankheiten, Schwerin.

In a randomized double-blind study involving 303 patients with alcoholic polyneuropathy the efficacy and tolerability of the combinations thiamine/pyridoxine, benfotiamine/pyridoxine, and the nucleotides of cytidine and uridine administered orally for 21 days were compared. Pain and paraesthesia, measured on a visual 10-cm-long analogue scale, as also pallaesthesia and the strength of the dorsiflexion and plantar flexors of the foot, clearly improved in all treatment groups. Clinically relevant differences in efficacy were not observed. All the drugs tested were well tolerated.

Eur J Oral Sci. 1996 Oct-Dec;104(5-6):583-8.

Prevention of etretinate-induced craniofacial malformations by vitamin B6 in the rat.

Jacobsson C, Granstrom G.

Department of Pedodontics, University of Gothenburg, Sweden.

The preventive effect of vitamin B6 on etretinate-induced malformations in pregnant Sprague-Dawley rats was studied. The etretinate-induced malformation was produced by intraperitoneal administration of 10 mg/kg etretinate at embryonal day 8.5. Vitamin B6 was administered as intramuscular injections at embryonal day 7.5 and 8.5. Vitamin B6 reduced the number and severity of facial clefts, micrognatia, meningocele, microtia and blood vessel anomalies. It is suggested that vitamin B6 induces suppressive effects on etretinate-induced teratogenesis when administered before or at the same time as the teratogen.

Z Ernahrungswiss. 1996 Sep;35(3):273-81.

[The effect of different vitamin B6 supplies on the vitamin B6 status (pyridoxine, pyridoxal and pyridoxamine) of the liver and the body of lactating rats]

[Article in German]

Benedikt J, Roth-Maier DA, Kirchgessner M.

Institut fur Ernahrungsphysiologie, Technische Universitat Munchen, Freising-Weihenstephan.

Eighty female Sprague-Dawley rats were fed a semisynthetic diet during gravidity which was supplemented with 5 mg vitamin B6 per kg diet. The daily food intake was 14 g. During the following lactation the rats were assigned to one of 10 vitamin B6 treatment groups (0, 3, 6, 9, 12, 15, 18, 36, 360 and 3,600 mg per kg diet). The feed was given ad libitum. At day 14 of lactation the rats were decapitated. Parameters for determination of the vitamin B6 status were concentration of pyridoxine, pyridoxal and pyridoxamine in liver and body analyzed by using HPLC. Body was defined without the gastroenteral tract that was divided into carcass (extrahepatic compartments without liver) and total body (extrahepatic compartments plus liver). The mean weight of liver was 13 g with a dry mass of 33%; there was no difference between the treatment groups. The vitamin B6 concentration was lowest in rats fed 0 mg vitamin B6/kg diet (5 micrograms/g fresh matter, FM) and highest in the rats fed 3600 mg vitamin B6/kg diet (10.9 micrograms/g FM). The total vitamin B6 consisted on the average of 38% pyridoxal and 62% pyridoxamine. This was only changed significantly at the highest supplementation level, where 20% pyridoxine were detected instead of pyridoxamine. The mean weight of carcass averaged 212 g at a dry matter content of 31%. The vitamin B6 concentration ranged in the treatment groups from 0 mg to 360 mg vitamin B6/kg diet between 2.1 micrograms/g FM and 2.8 micrograms/g FM. It was highest in the 3600 mg vitamin B6 treatment group at 7.5 micrograms/g FM. The total vitamin B6 consisted of 63% pyridoxal and 37% pyridoxamine. It was only significantly affected in the 3600 mg vitamin B6 treatment group, where also pyridoxine could be found in the amount of 56%. The results indicate that alimentary vitamin B6 supply had more influence on liver vitamin B6 concentration than on carcass concentration. Total body concentration is very similar carcass concentration, as 95% of vitamin B6 is located there. The suitability of the parameters by the evaluation of the vitamin B6 requirement was confirmed the comparison of two statistical methods. It is concluded that a vitamin B6 supply of 5 to 6 mg/kg diet is necessary to meet the requirements during lactation.

J Urol. 1996 Jun;155(6):1847-51.

A prospective study of the intake of vitamins C and B6, and the risk of kidney stones in men.

Curhan GC, Willett WC, Rimm EB, Stampfer MJ.

Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.

PURPOSE: The association between the intake of vitamins C and B6, and kidney stone formation was examined. MATERIALS AND METHODS: We conducted a prospective study of the relationship between the intake of vitamins C and B6 and the risk of symptomatic kidney stones in a cohort of 45,251 men 40 to 75 years old with no history of kidney calculi. Vitamin intake from foods and supplements was assessed using a semiquantitative food frequency questionnaire completed in 1986. RESULTS: During 6 years of followup 751 incident cases of kidney stones were documented. Neither vitamin C nor vitamin B6 intake was significantly associated with the risk of stone formation. For vitamin C the age-adjusted relative risk for men consuming 1,500 mg. daily or more compared to less than 250 mg. daily was 0.78 (95% confidence interval 0.54 to 1.11). For vitamin B6 the age-adjusted relative risk for men consuming 40 mg. daily or more compared to less than 3 mg. daily was 0.91 (95% confidence interval 0.64 to 1.31). After adjusting for other potential stone risk factors the relative risks did not change significantly. CONCLUSIONS: These data do not support an association between a high daily intake of vitamin C or vitamin B6 and the risk of stone formation, even when consumed in large doses.

Exp Clin Endocrinol Diabetes. 1996;104(4):311-6.

A benfotiamine-vitamin B combination in treatment of diabetic polyneuropathy.

Stracke H, Lindemann A, Federlin K.

Third Medical Department, University of Giessen, Germany.

In a double-blind, randomized, controlled study, the effectiveness of treatment with a combination of Benfotiamine (an Allithiamine, a lipid-soluble derivative of vitamin B1 with high bioavailability) plus vitamin B6/B12 on objective parameters of neuropathy was studied over a period of 12 weeks on 24 diabetic patients with diabetic polyneuropathy. The results showed a significant improvement (p = 0.006) of nerve conduction velocity in the peroneal nerve and a statistical trend toward improvement of the vibration perception threshold. Long-term observation of 9 patients with verum over a period of 9 months support the results. Therapy-specific adverse effects were not seen. The results of this double-blind investigation, of the long-term observation and of the reports in the literature support the contention that the neurotropic benfotiamine-vitamin B combination represents a starting point in the treatment of diabetic polyneuropathy.

J Gerontol A Biol Sci Med Sci. 1996 Jan;51(1):B100-7.

Dietary intakes of energy and water-soluble vitamins in different categories of aging.

van der Wielen RP, de Wild GM, de Groot LC, Hoefnagels WH, van Staveren WA.

Department of Human Nutrition, Wageningen Agricultural University, The Netherlands.

The dietary intakes of energy and the vitamins thiamin, riboflavin, B6, and C were assessed in four groups of elderly people, using the same modified dietary history method. The groups consisted of female nursing home residents (n = 40), people at admission to a nursing home (n = 21), free-living elderly people with a sedentary life style (n = 120), and physically active free-living elderly people (n = 66). Mean energy intake varied from 6.5 +/- 1.2 Megajoule (MJ)/day (nursing home residents) to 8.8 +/- 2.2 MJ/day (physically very active persons) in females and from 8.8 +/- 2.5 MJ/day (admission to nursing home) to 10.1 +/- 2.3 MJ/day (physically very active persons) in males. Dietary intakes of the selected vitamins were below the minimum requirements in almost half of the nursing home residents. However, the relative contribution of the various food groups to the dietary intake of these vitamins was similar in the four groups of elderly people. Stimulation of physical activity to increase energy requirements and use of foods with a high nutrient density may result in an improvement of dietary adequacy.

Am J Obstet Gynecol. 1995 Sep;173(3 Pt 1):881-4. Pyridoxine for nausea and vomiting of pregnancy: a randomized, double-blind, placebo-controlled trial.

Vutyavanich T, Wongtra-ngan S, Ruangsri R.

Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, Thailand.

OBJECTIVE: Our purpose was to determine the effectiveness of pyridoxine for nausea and vomiting of pregnancy. STUDY DESIGN: During an 11-month period 342 women who first attended Chiang Mai University Hospital antenatal clinic at < or = 17 weeks' gestation were randomized to received either oral pyridoxine hydrochloride, 30 mg per day, or placebo in a double-blind fashion. Patients graded the severity of their nausea by a visual analog scale and recorded the number of vomiting episodes over the previous 24 hours before treatment and again during 5 consecutive days on treatment. RESULTS: There was a significant decrease in the mean of posttherapy minus baseline nausea scores in the pyridoxine compared with that in the placebo group (t test, p = 0.0008). There was also a greater reduction in the mean number of vomiting episodes, but the differences did not reach statistical significance (p = 0.0552). CONCLUSION: Pyridoxine is effective in relieving the severity of nausea in early pregnancy.

Ned Tijdschr Geneeskd. 1995 Aug 19;139(33):1694-7.

[Pyridoxine-dependent epilepsy in an infant]

[Article in Dutch]

van Waarde WM, Tummers RF, Bosschaart AN, Hageman G.

Medisch Spectrum Twente, Enschede.

A newborn girl with seizures was, after repeated conventional anticonvulsive treatment, cured by pyridoxine administration. Pyridoxine-dependent seizures are an uncommon disease with autosomal-recessive heredity and a variable clinical picture. The prognosis may be favourable when diagnosis is made early. Confusion with perinatal asphyxia, and initial good response to usual anticonvulsive treatment can lead to delay in diagnosis.

Res Commun Mol Pathol Pharmacol. 1995 Aug;89(2):208-20.

Prevention of myocardial infarction by vitamin B6.

Ellis JM, McCully KS.

Titus County Memorial Hospital, Mt. Pleasant, Texas 75455, USA.

Vitamin B6 is effective in the treatment of carpal tunnel syndrome and related disorders in patients with vitamin B6 deficiency. Hyperhomocysteinemia, a risk factor for atherosclerosis, is associated with deficiencies of vitamin B6, folate, and cobalamin. Patients who were given vitamin B6 for carpal tunnel syndrome and other degenerative diseases were found to have 27% of the risk of developing acute cardiac chest pain or myocardial infarction, compared with patients who had not taken vitamin B6. Among elderly patients of the author (JE) expiring at home, the average age at death from myocardial infarction was 8 years later in those who had taken vitamin B6, compared with those who had not taken vitamin B6. The preventive effect of vitamin B6 on progression of coronary heart disease may be related to increased formation of pyridoxal phosphate, the coenzyme that is required for catabolism of the atherogenic amino acid, homocysteine.

Vet Hum Toxicol. 1995 Aug;37(4):342-5.

Pyridoxine as therapy in theophylline-induced seizures.

Glenn GM, Krober MS, Kelly P, McCarty J, Weir M.

Walter Reed Army Institute of Research, Washington, DC, USA.

Theophylline-induced seizures have significant morbidity and mortality and are difficult to treat. Theophylline therapy for asthma has been observed to depress plasma pyridoxal 5'-phosphate (PLP) levels which may decrease gamma-aminobutyric acid (GABA) synthesis and thereby contribute to seizures. We hypothesized that treatment with pyridoxine might prove beneficial in theophylline-induced seizures. One hundred thirty-nine mice were injected with 250 mg theophylline/kg ip and 89 mice were injected with 250-750 mg pyridoxine/kg ip as treatment. Decreased rates of seizure (42 vs 70%, p < 0.002) and death (29 vs 56%, p < 0.002) were observed. Six New Zealand White rabbits were given 115 mg theophylline/kg iv over 50 min followed by treatment with an iv bolus of 115 mg pyridoxine/kg, with subsequent continuous drip infusion of 230 mg/kg over 50 min. Serum theophylline levels and plasma PLP levels showed significant negative correlation prior to pyridoxine infusion with a mean peak theophylline level of 182 micrograms/ml and a mean low PLP level of 64 nM/L. Electroencephalogram (EEG) tracings were obtained before infusions, during theophylline infusion and during pyridoxine infusion. All 6 rabbits developed abnormal EEGs during theophylline infusion and all 6 rabbit EEG patterns returned to baseline during treatment with pyridoxine. These findings suggest that pyridoxine may partially reverse theophylline-induced central nervous system toxicity.

Lancet. 1995 Jul 8;346(8967):85-9.

Comment in: • Lancet. 1995 Sep 2;346(8975):635.

Effects of vitamin B12, folate, and vitamin B6 supplements in elderly people with normal serum vitamin concentrations.

Naurath HJ, Joosten E, Riezler R, Stabler SP, Allen RH, Lindenbaum J.

Department of Geriatric Medicine, University Witten-Heddecke, Velbert, Germany.

In a prospective, multicentre, double-blind controlled study, the effect of an intramuscular vitamin supplement containing 1 mg vitamin B12, 1.1 mg folate, and 5 mg vitamin B6 on serum concentrations of methylmalonic acid (MMA), homocysteine (HCYS), 2-methylcitric acid (2-MCA), and cystathionine (CYSTA) was compared with that of placebo in 175 elderly subjects living at home and 110 in hospital. Vitamin supplement and placebo were administered eight times over a 3-week period. Vitamin supplement but not placebo significantly reduced all four metabolite concentrations at the end of the study in both study groups. The maximum effects of treatment were usually seen within 5-12 days. Initially elevated metabolite concentrations returned to normal in a higher proportion of the vitamin than of the placebo group: 92% vs 20% for HYCS; 82% vs 20% for MMA; 62% vs 25% for 2-MCA; and 42% vs 25% for CYSTA. The response rate to vitamin supplements supports the notion that metabolic evidence of vitamin deficiency is common in the elderly, even in the presence of normal serum vitamin levels. Metabolite assays permit identification of elderly subjects who may benefit from vitamin supplements.

100: Lewis PJ. Pain in the hand and wrist. Pyridoxine supplements may help patients with carpal tunnel syndrome. BMJ. 1995 Jun 10;310(6993):1534. No abstract available. PMID: 7787619

Pediatrics. 1995 May;95(5):700-4.

Comment in: • Pediatrics. 1996 May;97(5):782. • Pediatrics. 1996 May;97(5):782-3.

Acute isoniazid neurotoxicity in an urban hospital.

Shah BR, Santucci K, Sinert R, Steiner P.

Department of Pediatrics, Children's Medical Center of Brooklyn, State University of New York 11203-2098, USA.

OBJECTIVES. To describe the presentation and treatment of acute isoniazid (INH) neurotoxicity appearing at an inner-city municipal hospital. DESIGN. Case series. PARTICIPANTS. Seven patients (eight patient visits) with an age range of 5 days to 14.9 years. RESULTS. At our institution, no children appeared with acute INH neurotoxicity in the period 1985 through 1990, whereas seven patients were treated from 1991 through 1993. This paralleled the rise in the number of children with tuberculous infection and disease seen at our institution, from an average 96 per year to 213 per year during these two time periods. All seven patients were receiving INH daily for tuberculosis (TB) prophylaxis. Accidental ingestion (five episodes) and suicidal attempts (three episodes) accounted for these visits. The total amount ingested range from 14.3 to 99.3 mg/kg (mean, 54 mg/kg). All but one patient presented with afebrile seizures. One patient presented twice with seizures. Acute INH neurotoxicity was not suspected on the first admission; however, when readmitted 4 weeks later with another seizure, the diagnosis of acute INH neurotoxicity was made. INTERVENTION. Intravenous pyridoxine was used in five episodes. Because it was not a stocked item in our pediatric emergency cart (as well as at another hospital, necessitating a transfer of a patient with refractory seizures to our hospital), the average delay was 5.8 hours (range, 1.3 to 13 hours) before it was given. Two patients with refractory seizures failed to respond to anticonvulsants, and their seizures were controlled only after parenteral pyridoxine. CONCLUSIONS. We have seen an increased incidence of acute INH neurotoxicity because of the resurgence of TB in New York City. Others as well may see a similar rise based on local trends in TB infection and disease. Acute INH toxicity should be suspected in children presenting with seizures with or without fever. In patients with a known access to INH, seizures should be considered to be caused by INH toxicity unless proved otherwise. Parenteral pyridoxine, the specific antidote for INH-induced refractory seizures, should be readily available in every emergency department in the areas similarly experiencing increasing trends of TB.

Am J Clin Nutr. 1995 Mar;61(3):571-6.

Pyridoxine supplementation protects mice from suppression of contact hypersensitivity induced by 2-acetyl-4-tetrahydroxybutylimidazole (THI), ultraviolet B radiation (280-320 nm), or cis-urocanic acid.

Reeve VE, Bosnic M, Boehm-Wilcox C, Cope RB.

Department of Veterinary Pathology, University of Sydney, Australia.

Evidence exists implicating the epidermal ultraviolet B (UVB) photoproduct cis-urocanic acid as an immunogenic mediator of the systemic suppression of T cell-mediated immunity by UVB exposure. Cis-urocanic acid appears to act via histamine receptor pathways, and histamine receptor antagonists and other imidazole ring compounds may modify its immune suppressing action. A component of the food coloring substance ammonia caramel, 2-acetyl-4-tetrahydroxybutylimidazole (THI), which is known to cause lymphopenia in rats, appears to suppress immunity by a similar pathway when the contact hypersensitivity reaction has been the immune function assay in mice. The induction of lymphopenia in rats by THI is inhibited by the vitamin pyridoxine. This study demonstrates that the suppression of contact hypersensitivity in mice by UVB radiation, cis-urocanic acid, or THI is strongly inhibited by supplemental pyridoxine, fed at 30 mg/kg diet, in comparison with the normal diet, which supplies 7 mg pyridoxine/kg diet. These results suggest that pyridoxine competes with cis-urocanic acid and THI for the same binding site or receptor, which we postulate to be a histamine-like T lymphocyte receptor, and that a role may exist for the control of photoimmunosuppression by this vitamin.

Am J Hum Genet. 1995 Mar;56(3):616-22.

Pyridoxine-responsive gyrate atrophy of the choroid and retina: clinical and biochemical correlates of the mutation A226V.

Michaud J, Thompson GN, Brody LC, Steel G, Obie C, Fontaine G, Schappert K, Keith CG, Valle D, Mitchell GA.

Service de genetique medicale, Hopital Ste-Justine, Montreal, Quebec, Canada.

We discovered the missense mutation, A226V, in the ornithine-delta-aminotransferase (OAT) genes of two unrelated patients with gyrate atrophy of the choroid and retina (GA). One patient, who was a compound for A226V and for the premature termination allele R398ter, showed a significant (P < .01) decrease in mean plasma ornithine levels, following pyridoxine supplementation with a constant protein intake: 826 +/- 128 microM (n = 5; no pyridoxine supplementation) versus 504 +/- 112 microM (n = 6; 500 mg pyridoxine/d) and 546 +/- 19 microM (n = 6; 1,000 mg pyridoxine/d). In extracts of fibroblasts from a second GA patient homozygous for A226V and from Chinese hamster ovary cells expressing an OAT-cDNA-containing A226V, we found that OAT activity increased from undetectable levels to approximately 10% of normal when the concentration of pyridoxal phosphate was increased from 50 to 600 microM. A226V is the fourth disease-causing pyridoxine-responsive human mutation to be reported.

Eur J Clin Invest. 1995 Mar;25(3):176-81.

Hyperhomocysteinaemia and endothelial dysfunction in young patients with peripheral arterial occlusive disease.

Van den Berg M, Boers GH, Franken DG, Blom HJ, Van Kamp GJ, Jakobs C, Rauwerda JA, Kluft C, Stehouwert CD.

Department of Vascular Surgery, Free University Hospital, Amsterdam, The Netherlands.

Hyperhomocysteinaemia, defined as an abnormally high plasma homocysteine concentration after an oral methionine load, is common in young (< or = 50 years) patients with peripheral arterial occlusive disease. It is thought to predispose to atherosclerosis by injuring the vascular endothelium. Treatment with pyridoxine and/or folic acid may lower plasma homocysteine levels. In mildly hyperhomocysteinaemic patients with peripheral arterial occlusive disease, we studied the effect of daily treatment with pyridoxine (250 mg) plus folic acid (5 mg) on homocysteine metabolism (i.e. plasma concentrations in the fasting state and after methionine loading, in 48 patients) and on endothelial function (in 18 patients). Endothelial function was estimated as the plasma concentrations of the endothelium-derived proteins, von Willebrand factor (vWF), thrombomodulin (TM), and tissue-type plasminogen activator (tPA). At baseline, fasting homocysteine levels were above normal in 24 of the 48 patients (50%); post-load levels, by definition, were above normal in 100% of patients. After 12 weeks of treatment, fasting and post-load levels were normal in 98 and 100% of patients, respectively. Endothelial function was assessed in 18 patients who completed 1 year of treatment. At baseline, median vWF (235%) and TM (57.1 ng mL-1) levels were above normal. At follow-up, vWF levels had decreased to 170% (P = 0.01) and TM levels had decreased to 49 ng mL-1 (P = 0.04). tPA levels were normal at baseline and did not change. Endothelial dysfunction is present in young patients with peripheral arterial occlusive disease and hyperhomocysteinaemia. Pyridoxine plus folic acid treatment normalizes homocysteine metabolism in virtually all patients, and appears to ameliorate endothelial dysfunction.

J Child Neurol. 1995 Mar;10(2):143-7.

Medical treatment of West syndrome in Japan.

Watanabe K.

Department of Pediatrics, Nagoya University School of Medicine, Japan.

Although corticotropin (ACTH) is still the most effective drug for the treatment of West syndrome, a variety of other treatment modalities have been tried because of corticotropin's frequent and sometimes serious side effects. A recent survey on the treatment of this devastating disorder by Japanese child neurologists disclosed different therapeutic approaches from those taken by American or European child neurologists. Most Japanese child neurologists use vitamin B6 as the first agent and corticotropin as the third or second drug. Moreover, the dosage of corticotropin used by them is considerably smaller. Therefore, the current status of medical treatment of West syndrome is reviewed, especially comparing Japan with other countries.

Ann Nutr Metab. 1995;39(5):285-90.

Effect of pyridoxine and magnesium on stress-induced gastric ulcers in mice selected for low or high blood magnesium levels.

Henrotte JG, Aymard N, Allix M, Boulu RG.

Institut de Chimie des Substances Naturelles, CNRS, Gif-sur-Yvette, France.

Gastric ulcers were induced by immobilization in adult female mice with genetically low (MGL) or high (MGH) blood magnesium levels, obtained by selective breeding at the CSAL-CNRS (Orleans, France). All animals, fed with the same standard diet rich in magnesium, were divided into four groups of 20 animals and injected subcutaneously every 2 days for 10 days with isotonic saline (group 1), pyridoxine chlorhydrate 1.11 mg/kg in saline (group 2), magnesium lactate 149 mg/kg in saline (group 3) or both pyridoxine and magnesium (group 4). Subsequently, animals were submitted to a complete fast and an immobilization stress for 17 h. Then, they were sacrificed and the gastric mucosa was dissected for ulcer count. Among the controls (group 1), the mean number of gastric ulcers per mouse was significantly larger in the MGL than in the MGH line (p = 0.0003). In the MGH line, no significant differences were observed between control and treated groups. In the MGL line, pyridoxine associated or not with magnesium (groups 2 and 4) significantly reduced the mean number of ulcers. Magnesium treatment alone (group 3) had little effect. These results can be compared with the greater vulnerability to stress previously observed in Swiss mice fed with a magnesium-deficient diet. However, in this latter group, the number of stress ulcers was reduced not only by pyridoxine but also by the sole magnesium treatment, contrary to our present findings in MGL mice.